2 Objectives State the ways of transmission of the disease to the fetus Describe the pathogenesis pathway for congenital toxoplasmosisDiscuss the clinical significance of the infectionDefine significance of detection of IgM and IgGDiscuss different methods for management the disease in mother and infantDescribe the main aspects of prevention and control .Mode transmission of congenital toxoplasmosisPathogenesis of congenital toxoplasmosisSignificance of congenital toxoplasmosisTreatment and management of congenital toxoplasmosis
3 What causes Toxoplasmosis? The protozoan Toxoplasma gondii, is a coccidian, obligate, intracellular parasite responsible for zoonotic infections in man and other mammalsT gondii is one of the most common human parasites in the world. The organism was first discovered in the gundi, a North African rodent.
4 Congenital Toxoplasmosis Congenital transmission happens when the mother is exposed to infection by Toxoplasma gondii for first time while she is pregnant.The effect on the foetus depends on the time of infection during pregnancy.
5 Host Definitive host (final host):-Only Cat Accidental host (Non specific host) :-All mammals including Man, Farm animals,Rat,Mice and Avian (harbor asexual stages).
7 Site of infectionIn definitive host:- Intra-cytoplasmic epithelial cells of small intestine.In accidental host ( Man):- Reticuloendothelial system , brain and retinal cells.
8 Primary Transmission of Toxoplasmosis Ingesting cystsRaw or undercooked meatEspecially pork, muttonIngesting oocystsAccidental ingestion of feline fecesContaminated dirt at playgrounds or sandboxesHands contaminated when changing litter boxesPrimary human infection may be acquired in two ways: 1) ingestion of undercooked infected meat containing Toxoplasma cysts; and 2) ingestion of the oocyst from fecally contaminated hands or food..The strongest risk factors for infection are eating raw or undercooked lamb, beef, or other meat, such as game or pork. In infected animals, the parasites form tissue cysts in both skeletal and non-skeletal muscle; but non-skeletal muscle such as the heart, diaphragm, and tongue usually have a higher density of cysts than skeletal muscle. These cysts may remain throughout the life of the host.Contact with soil or vegetables or fruit contaminated with soil is another common means of acquiring infection. More rarely, tasting raw meat during preparation of meals, eating salami, and drinking unpasteurized milk have been associated with T. gondii infection in humans.A recent European study* of acute toxoplasmosis among pregnant women found that between 30% and 63% of infections were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact.Contact with cats, kittens, cats’ feces, or cats who hunt for food has not been found to be a risk factor for infection.Oocysts may be ingested when cat feces are accidentally ingested, usually via contaminated hands. However, oocysts are sometimes transferred from cat feces to food by insects such as flies and cockroaches.* Cook AJ, Gilbert RE, Buffolano W, et al. Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis. BMJ 2000 Jul 15;321(7254):142-7.
9 Ways of InfectionOral intake of raw or rare ("under-cooked") meat or of contamination with cats feces or consumption of contaminated vegetables, fruits, and salad, ... A fresh maternal infection during pregnancy can lead to an infection of the placenta.Congenital Toxoplasmosis results from transplacental infection of the fetus during pregnancy.
10 Transmission Cycle DEFINITIVE HOST (cat) Cysts ingestedby catUnsporulated oocyst passed in fecesSporulatedoocystIntermediate host ingests oocysts infeed, water, or soilCysts containing bradyzoitesin tissues of intermediate hostsINTERMEDIATE HOSTSContamination offood and waterIngests cystsin infected meatInfection of fetusTachyzoitestransmittedthrough placentaCats are the only definitive hosts of T. gondii. They can become infected by ingesting any of the three forms: bradyzoites, oocysts, or, rarely, tachyzoites. After infection, they shed oocysts in large quantities (up to 10 million oocysts per day) but only for the first 3-15 days after becoming infected; upon acquiring immunity shedding ceases.In fresh feces, oocysts are not sporulated and are not infective. Sporulation occurs after 1–5 days, depending on the temperature, humidity, and aeration, and produces two sporocytes, each containing 4 sporozoites. It is these sporocytes that contaminate soil in which infected cats have defecated.The extraintestinal cycle begins when another host ingests a sporulated oocyst or animal tissue containing cysts filled with bradyzoites. Tachyzoites, the proliferative forms, develop and are carried via lymphatics and bloodstream throughout the body. The tachyzoites invade nucleated cells of any tissue but preferentially parasitize muscle and nervous tissue.In pregnant women, the rapidly dividing tachyzoites may cross the placenta and infect the fetus.
11 life-cycle for Toxoplasma gondii The asexual stages of T. gondii can cause diseasein humans and most animals .There are two asexual forms. The first form, calledtachyzoite,( fast replicating form) can invade all types of cells and divides rapidly, leading to cell death .The second form, called the bradyzoite, dividesslowly and forms cysts, most prominently inmuscle and brain. Tissue cysts can be ingested by a cat where they undergo sexual reproduction and oocyst formation.
12 Toxoplasma gondii – Life cycle OocystBradyzoiteTachyzoite
13 Transplacental Transmission of Toxoplasmosis Occurs when primary infection occurs during pregnancyRisk and severity vary depending on the trimester in which infection occurs1st trimester: 15% of fetuses infected2nd trimester: 30% of fetuses infected3rd trimester: 60% of fetuses infectedBut the earlier in pregnancy the infection occurs, the more severe the fetal infectionTransplacental transmission can occur when a pregnant woman contracts primary toxoplasmosis. The risk and severity of the baby’s infection depend partly on the timing of the mother’s infection. Studies indicate that, 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. However, the earlier in pregnancy the infection occurs, the more severe the fetal infection.
14 Congenital Toxoplasmosis A)Frist trimester…… Abortion B)Second trimester…Stillbirth C)Third trimester…Infection may be present as:- Hydrocephaly, Neonatal jaundice . Mental retardation.
15 Congenital Toxoplasmosis The consequences of the infection of the fetus can be very different: between subclinical and very serious.Abortion Overt disease. The symptoms vary widely, the classical triad of Congenital Toxoplasmosis is HydrocephalusIntracranial calcificationChorioretinitis
16 Complications of toxoplasmosis Complications list for Toxoplasmosis:The list of complications that have been mentioned in various sources for Toxoplasmosis includes:Complications of a pregnant women becoming newly infected with toxoplasmosis:Spontaneous abortion - in affected pregnant womenStillbirth - in affected pregnant womenFetal or newborn complications of a pregnant woman with toxoplasmosis:Congenital toxoplasmosis - passed to newborn by infected mother by cross-placental contagion.Neonatal jaundiceNewborn brain disordersNewborn eye disorders
17 Some pictures of symptoms of Congenital Toxoplasmosis: Hydrocephalus
20 Diagnosis of Toxoplasmosis Diagnosis of Toxoplasmosis: pregnant womenSerological diagnosis in case ofmaternal (swollen lymphatic glands, fever) orfetal symptoms (detected in ultrasound) :Serological screening: to detect asymptomatic infections
21 DiagnosisA)Clinical diagnosis:- Depends on history and clinical picture.B)Laboratory diagnosis:-1- Direct methods :-Biobsy2-Indirect methods :-a)Toxoplasmin skin testb )Serological tests (Sabin Feldman Methylene Blue Dye Test ,IHAT ,ELISA, IFAT).
22 Immunonological diagnosis When an infection happens, IgG and IgM get "positive". IgM are "positive" during acute infection and stay positive for a limited time (depending the methods of test You use). (Maybe 6 months to a year) IgG-titers rise during an acute infection, sink slowly again, but stay positive, and protect against another parasitaemia (and protects so the unborn baby).
23 DIAGNOSISIgG appear within 2 weeks of infection, peak in 6-8 wks, then decline over next 2 years, but detectable for lifeIgM within first week and decline within a few months, however can persist for years after initial infection (therefore can not be used to confirm recent or acute infection)Acute infection can be confirmed by culture, documented seroconversion, or 2-fold rise in antibody level
24 Toxoplasmosis – Diagnosis Significance of detection of IgM and IgG Antibody testing
25 Fetal diagnosis in case of maternal infection during pregnancy When a pregnant woman has got an infection, there is the possibility, that she passes the infection on to her baby. To know, if the fetus (unborn baby) is infected helps tofind adequate treatment (for mother and fetus)start treatment of the baby immediately after birth
26 Fetal diagnosis in case of maternal infection during pregnancy if the infection occurred during pregnancy: anti-parasitic drugs should be taken until birth to reduce the risk of a fetal infection and the fetus (unborn baby) should be tested
27 Pediatric diagnosisSerological tests of a blood sample of the newborn baby (or of an umbilical cord blood sample taken by the midwife) can help to find the diagnosis of Congenital Toxoplasmosis. IgG are passed from the mother to the baby through the placenta and could be of maternal origin. IgM cannot pass the placenta. If they are found infection of the baby is proofed. But: not all infected babies produce IgM, that mean, that the absence of IgM does not exclude Congenital Toxoplasmosis! In these cases the serological diagnosis of Toxoplasmosis can be performed by a follow-up. IgG-titers of maternal origin sink (half-life period about a month). Persisting (or rising) IgG proof congenital infection of the baby! Therefore serological testing should be repeated until IgG turns negative, exclusion of Congenital Toxoplasmosis cannot be done before that!
31 Toxoplasmosis prevention of Congenital. Primary prevention is an information about the ways of infection (cats, raw meet) to avoid ingestion or inhalation. This is important for all pregnant women who are "seronegative"Secondary prevention is the detection of infected women during pregnancy to start treatment before the fetus gets infected.Tertiary Prevention is the treatment of infected children to reduce or avoid symptoms.