Toxoplasmosis

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TOXOPLASMOSIS:

TOXOPLASMOSIS

Notifiable Parasitic Diseases:

Notifiable Parasitic Diseases Reportable in CA Amebiasis Anisakiasis Babesiosis Cryptosporidiosis Cysticercosis Echinococcosis Giardiasis Malaria Toxoplasmosis Trichinosis Not reportable in CA Zoonotic ascarids Baylisascaris procyonis Toxocara spp. Cercarial dermatitis

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Toxoplasma gondii has very low host specificity, and it will probably infect almost any mammal. It has also been reported from birds, and has been found in virtually every country of the world. Like most of the Apicomplexa, Toxoplasma is an obligate intracellular parasite. Its life cycle includes two phases called the intestinal (or enteroepithelial) and extraintestinal phases. Introduction

What is toxoplasmosis?:

What is toxoplasmosis ? Toxoplasmosis is an infection that can threaten the health of an unborn child Toxoplasma gondii is a sporazoan of the subclass Coccidia. The only species is Gondii. It exists in three forms--tachyzoites (trophozoites), tissue cysts, and oocytes. is a common intracellular protozoan which infects most species of warm-blooded animals, They span many vertebrates from rodents to domestic farm animals (including birds) to humans throughout the world. A Zoonotic Infection of Humans Normal cycle in cats (lions, tigers and puddy tat ) enteroepithelial (EE) cycle in definitive host asexual and sexual division is intracellular in MEC oocytes become infective after passage in feces (Oocytes do not become infectious until they sporulate. Depending on conditions such as temperature, sporulation occurs 2 to 21 days after the oocyte is excreted in the feces ) tissue cycle in intermediate/carrier hosts all vertebrates are potential hosts (mice, birds,, ?) motile, disease producing phase = tachyzoites non-motile “slow” phase in pseudocyst = bradyzoites

Toxoplasmosis:

Toxoplasmosis Single-cell organism Global Distribution Reservoir host - Cats Uncommon cause of human disease Except: pregnant women & fetus Immunocompromised persons

Sources of infection:

Sources of infection Source of all oocytes ... Domestic (cats,dogs) and wild (zoo) cats ( Cats are the only known full-life-cycle host of the protozoan) parasite Rodents :rats Persist in environment (soil) if moist reservoir of infective oocytes Many intermediate hosts reservoir of infective tissue cysts( farm animals—cattle,sheep,rabbit) Cycle in humans (an accidental host) Infected by ingesting infective oocytes (in >4 day old cat feces) by ingesting tachyzoites or bradyzoites in rare meat by receiving blood or tissues with “-zoites” CONGENITALLY by transplacental tachyzoites Proliferative stages in humans tachyzoites result from all infective stages bradyzoites predominate within pseudocysts as IgG

Toxoplasmosis:

Toxoplasmosis

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The intestinal phase occurs in cats only (wild as well as domesticated cats) and produces "oocysts." The extraintestinal phase occurs in all infected animals (including cats) and produces "tachyzoites" and, eventually, "bradyzoites" or "zoitocysts." The disease toxoplasmosis can be transmitted by ingestion of oocysts (in cat feces) or bradyzoites (in raw or undercooked meat).

Toxoplasma: Animal Disease:

Toxoplasma: Animal Disease Infects all animals, including birds Cats infected by ingestion of cyst (feces or raw meat) Asymptomatic Shed for 1-2 weeks No treatment necessary Diagnostic tests Serology Do NOT routinely perform serologic test of cats Cannot determine whether excreting oocysts Microscopic evaluation of feces

Toxoplasma: Human Transmission:

Toxoplasma: Human Transmission Infection in humans typically through ingestion Raw/undercooked meat Estimated to occur in ½ of T. gondii infections in U.S. Parasite isolated from 32% pork chops, 4% lamb chops (1960s) Ingestions of oocyst from cat feces or soil Water or food contaminated with oocysts Also transplacental transmission Mother acquires infection during gestation

Toxoplasma: At Risk for Severe Disease:

Toxoplasma: At Risk for Severe Disease Congenitally infected fetuses and newborns Estimated 400-4000 cases each year in the U.S. Immunologically impaired individuals, most commonly with defects in T-cell-mediated immunity Hematologic malignancies Bone marrow and solid organ transplants AIDS, e.g. leading to toxoplasmic encephalitis

Toxoplasma gondii:

Toxoplasma gondii Tachyzoites Cyst in brain tissue

Morphology:

Morphology The intracellular parasites (tachyzoite) are 3x6µ, crescent shaped organisms that are enclosed in a parasite membrane to form a cyst measuring 10-100 µ in size. Cysts in cat feces (oocysts) are 10-13 µ in diameter

Toxoplasma - oocysts:

Toxoplasma - oocysts Survives in the environment for several months Resistant to disinfectants, freezing, and drying Killed by heating to 70°C for 10 minutes Sporulation 1-5 days

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Another example of Toxoplasma gondii tachyzoites.

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Intracellular tachyzoites of Toxoplasma gondii .

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A zoitocyst of Toxoplasma gondii filled with bradyzoites; this zoitocyst is in cardiac muscle.

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A sporulated oocyst of Toxoplasma gondii . The oocyst contains two sporocysts, each of which contain four sporozoites. Thus, they resemble the oocysts of Isospora sp. Only cats will produce and pass Toxoplasma oocysts; approximate diameter = 10 µ m.

Clinical pictures(difficult diagnosis):

Clinical pictures (difficult diagnosis) Toxoplasma gondii can cause a wide spectrum of disease after infecting a new host, including acute, latent, and reactivated disease as well as congenital disease Congenital tox Maternal tox + inapparent —subclinical--usually is asymptomatic —most of cases + apparent ( 10-20 %)—not specific = generalised tox —flue like illness- fever,fatigue,weakness,malaise = lymphatic tox- --fever,generalised lymphadenopathy(retroperitoneal, mesentric{abdominal pain},lumbar,occiptal), liver and spleen enlargement The lymphadenitis may wax and wane for months and finally resolve spontaneously. It is commonly mistaken with infectious mononucleosis). = neurological tox- --encephalopathy,chorioretinitis = exanthematous tox- --generalised maculopapular erythramatous patches = Ocular tox- -- eye pain, Photophobia, blurred vision, scotoma ("blind spot"), chorioretinitis, Retinitis, blindness = The acute acquired form however, can be a fulminating disease with an erythematous rash, fever, malaise, myositis, dyspnea, acute myocarditis,and encephalitis. Outcome can be fatal, but this form of toxoplasmosis is rare

Symptoms:

Symptoms Although Toxoplasma infection is common, it rarely produces symptoms in normal individuals. Its serious consequences are limited to pregnant women and immunodeficient hosts. Congenital infections occur in about 1-5 per 1000 pregnancies of which 5-10% result in miscarriage, 8-10% result in serious brain and eye damage to the fetus, 10-13% of the babies will have visual handicaps. Although 58-70% of infected women will give a normal birth, a small proportion of babies will develop active retino-chorditis or mental retardation in childhood or young adulthood.

Congenital toxoplasmosis:

Congenital toxoplasmosis

Congenital infections:

Congenital infections Conditions of transmission [nfection during parasitemia – in unexposed mother with an active primary infection during pregnancy or previously expose d mother before pregnancy with immune compromise eg : (AIDS ) very rare tachyzoites cross placental barrier fetus becomes infected only about 40% of time the risk of the baby's infection depend partly upon the timing of the mother's infection. when mothers are infected in the first trimester , 15 percent of fetuses become infected, as compared to 30 percent in the second trimester and 65 percent in the third trimester. severity of the baby's infection the earlier in pregnancy the infection occurs, the more severe the fetal infection. When the mother is infected between 10 to 24 weeks gestation, the risk for severe problems in the newborn is about 5 to 6 percent. When the mother is infected late in a pregnancy, the chance that the baby will have problems is very small .

Congenital Toxoplasmosis:

Congenital Toxoplasmosis Two types: Asymptomatic (inapparent) Congenital Toxo 60% of infected may suffer from Long Term Sequella up to 90 percent of infected babies appear normal at birth, 80 to 90 percent will develop sight-threatening eye infections months to years after birth. About 10 percent will develop hearing loss and/or learning disabilities Symptomatic Congenital Toxo 40% of infected--About one in 10 infected babies has a severe Toxoplasma infection that is evident at birth. These newborns often have severe eye infections, an enlarged liver and spleen, jaundice (yellowing of the skin and eyes), pneumonia and other problems. Some die within a few days of birth. Those who survive sometimes suffer from mental retardation, severely impaired eyesight, cerebral palsy, seizures and other problems. more likely if mother infected in 1st/2nd Trimester Severe damage to fetus = stillbirth or abortion

Toxoplasmosis – ocular lesions:

Toxoplasmosis – ocular lesions

Toxo Diagnosis:

Toxo Diagnosis Morphologic tachyzoites in circulating WBC, bone marrow, lung, spleen, brain ? histopathologic examination Culture or animal inoculation (rare) Isolation of parasites from blood or other body fluids, by intraperitoneal inoculation into mice or tissue culture. The mice should be tested for the presence of Toxoplasma organisms in the peritoneal fluid 6 to 10 days post inoculation; if no organisms are found, serology can be performed on the animals 4 to 6 weeks post inoculation. Serologic (mainly) Detection of parasite genetic material by PCR , especially in detecting congenital infections in utero.

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Tests which employ whole parasites include the dye test (Sabin-Feldman Dye Test (DT) direct agglutination and the fluorescent antibody test, whilst tests that use disrupted parasites as an antigen source include ELISA, latex agglutination, indirect haemagglutination and complement fixation.

Serologic Diagnosis of Toxo:

Serologic Diagnosis of Toxo unreliable in immunodeficient (AIDS) pts normally IgM and IgG rise simultaneously IgG - persists for years IgM - undetectable after “cure” elevated IgM titer is diagnostic of recent infection in persons with normal immunity disseminated infection may exist in AIDS pts without demonstrable titer A negative IgG or IgM test excludes Diagnosis both should be + if acutely infected If IgG screening is + then do IgM test a + IgM test confirms acute toxoplasmosis or current Toxoplasma infection ( measure IgM antibodies, have low specificity and the reported results are frequently misinterpreted. In addition, IgM antibodies can persist for months to more than one year) Submit IgG positive sera to CDC for IgM testing for diagnosis of acute Toxo

Polymerase Chain Reaction (PCR) :

Polymerase Chain Reaction (PCR) PCR amplification is used to detect T. gondii DNA in body fluids and tissues. It has been successfully used to diagnose congenital, ocular, cerebral and disseminated toxoplasmosis. PCR performed on amniotic fluid has revolutionized the diagnosis of fetal T. gondii infection by enabling an early diagnosis to be made, thereby avoiding the use of more invasive procedures on the fetus. PCR has allowed detection of T. gondii DNA in brain tissue, cerebrospinal fluid (CSF), vitreous and aqueous fluid, bronchoalveolar lavage (BAL) fluid, urine, amniotic fluid and peripheral blood.

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IgG levels begin to rise 1 or 2 weeks after infection. Peak levels are reached in 6 to 8 weeks, then gradually decline over a period of months or even years. Low levels of IgG are generally detectable for life. Detectable levels of IgM antibody appear immediately before or soon after the onset of symptoms. IgM levels normally decline within 4 to 6 months, but may persist at low levels for up to a year immunocompromised individuals may not produce any IgM. Antibody levels do not correlate with severity of illness

Prenatal Management of Congenital Toxoplasmosis:

Prenatal Management of Congenital Toxoplasmosis Identified acute maternal Toxo infection tested fetal blood for Toxo (culture/serology) confirmed fetal CNS involvement (ultrasound) spiromycin for acutely Toxo in affected mother added pyrimethamine /sulfadiazine if fetus is affected TTT reduced congenital symptoms by 70% 2 of 15 children infected in utero had chorioretinitis (While these results are encouraging, the safety, effectiveness and feasibility of prenatal toxoplasmosis screening, diagnosis and treatment are not yet established. For these reasons, in the United States, most pregnant women are not screened for toxoplasmosis. )

Toxoplasmosis TTT:

Toxoplasmosis TTT Drugs of choice for pregnant women or immunocompromised persons: Spiramycin or Pyrimethamine plus Sulfadiazine Treatment pyrimethamine (Daraprim) + sulfadiazine side effects( skin rashes and leukopenia ) are common in AIDS pts High-dose therapy is continued for 4-6 weeks, and lower dose maintenance therapy is given thereafter. Maintenance therapy can be discontinued in patients who have completed the course of initial treatment and are without symptoms, Spiramycin alone before 26 weeks pyrimethamine + clindamycin or dapsone Clindamycin, a similar drug, is often substituted for sulfadiazine in patients with sulfa allergy NB : Pyrimethamine can cause low blood counts in some people.  To counter the possible effects of pyrimethamine on the bone marrow, another drug called leucovorin (folinic acid) is given along with pyrimethamine Prophylaxis –in the primary prevention of toxoplasmosis in persons with HIV who have dormant or latent infection TMP-SMX - trimethoprim-sulfamethoxazole pyrimethamine plus folinic acid dapsone + pyrimethamine

Treatment::

Treatment: NO TTT in Asymptomatic Because it is self limiting disease Exept in children to prevent retinal inflammation In healthy people, infection with Toxoplasma gondii , leads to the production of sarcocysts in various tissues and immunity to additional infections. Thus, an infected but asymptomatic person in good health generally does not need treatment. TTT of pregnant women is controversy because of toxicity of medication but TTT is still advocated

Drugs:

Drugs Spiromycin(rovamycin) Daily for rest of pregnancy OR 3weeks ttt then 1 week rest then repeat for rest of pregnancy OR 1 week ttt then 1 week rest then repeat for rest of pregnancy OR 3 weeks ttt

Treatment of Infected Newborns:

Treatment of Infected Newborns Infected babies should be treated as soon as possible after birth with pyrimethamine and sulfadiazine which, as mentioned earlier, can help prevent or reduce the disabilities associated with toxoplasmosis.

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Routine neonatal screening for toxoplasmosis identifies congenital and early subclinical infections. Treatment may reduce the severe long term sequelae.

Prevention and Control:

Prevention and Control Education Avoid ingestion of and contact with cysts or sporulated oocysts Cook meat to well done with no visible pink in center Wash hands thoroughly after handling raw meat or vegetables Avoid areas with cat feces Change litter every day (before sporulation) Wear disposable gloves when disposing of cat litter, working in garden, cleaning child’s sandbox Serologic screening for pregnant women

Immunology:

Immunology Both humoral and cell mediated immune responses are stimulated in normal individuals. CMI is protective and humoral response is of diagnostic value.

Immunity to TG:

Immunity to TG Active infection normally occurs only once in a lifetime. Although the parasite remains in the body indefinitely latent infections usually persist for life ( the immune system reacts against the parasite, causing the parasite to hide in an inactive form (cyst) in tissues throughout the body (usually the skeletal muscles and the brain). . , it generally is harmless and inactive unless the immune system is not functioning properly in immuno-compromised host -- the parasite can reactivate and cause serious illness, characterized by inflammation of the brain If a woman develops immunity to the infection at least six to nine months before pregnancy, there rarely is any danger of passing it on to her baby because immunity is developed to it

CD4 Cell Counts:

CD 4 Cell Counts T-cells (or T-lymphocytes) are white blood cells that play important roles in the immune system. There are two main types of T-cells. One type has molecules called CD4 on its surface; these ‘helper’ cells orchestrate the body’s response to certain micro-organisms such as viruses. The other T-cells, which have a molecule called CD8, destroy cells that are infected and shut down the immune response once the infection has been dealt with. Doctors use a test that ‘counts’ the number of CD4 cells in a cubic millimetre of blood to identify how strong the immune system and helps predict the risk of complications and debilitating infections A normal count in a healthy, HIV negative adult can vary, but is usually between 600 and 1200 CD4 cells/mm3. when a person is first diagnosed as part of a baseline measurement. test should be repeated about four weeks after starting anti-tox therapy. a CD4 count should be performed every three to four months thereafter.

Prevention of Toxoplasmosis:

Prevention of Toxoplasmosis Previous exposure prevents congenital Toxo transmission - buy a cat ! education avoiding exposure to the parasite, mostly by simple hygienic measures. avoid exposure to oocytes no cats or cat feces ! no raw meat for you or your kitty ! keep house cats inside - avoid stray cats ! let anyone empty the cat box ! cover the kid’s sand box ! wear gloves in the garden, wash your hands! wash all fruits and vegetables, wash hands carefully after handling raw meat, fruit, vegetables, and soil pregnant women should cook their meat until it is no longer pink and the juices run clear

Recommendations:

Recommendations An IgM test is used to help determine whether a patient has been infected recently or in the distant past. Because of the significant potential of misinterpreting a positive IgM test result, confirmatory testing should be performed. Despite the wide distribution of commercial test kits to measure IgM antibodies, these kits often have low specificity and the reported results are frequently misinterpreted. In addition, IgM antibodies can persist for months to more than one year.

Thank You:

Thank You