1. Congenital Toxoplasmosis
Dr.Omar H.Amer
Prof.of Parasitology

2. Objectives State the ways of transmission of the disease to the fetus
Describe the pathogenesis pathway for congenital toxoplasmosis
Discuss the clinical significance of the infection
Define significance of detection of IgM and IgG
Discuss different methods for management the disease in mother and infant
Describe the main aspects of prevention and control .
Mode transmission of congenital toxoplasmosis
Pathogenesis of congenital toxoplasmosis
Significance of congenital toxoplasmosis
Treatment 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 mammals
T 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).

6. What causes Toxoplasmosis?

7. Site of infection
In 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 cysts
Raw or undercooked meat
Especially pork, mutton
Ingesting oocysts
Accidental ingestion of feline feces
Contaminated dirt at playgrounds or sandboxes
Hands contaminated when changing litter boxes
Primary 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 Infection
Oral 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 ingested
by cat
Unsporulated oocyst passed in feces
Sporulated
oocyst
Intermediate host ingests oocysts in
feed, water, or soil
Cysts containing bradyzoites
in tissues of intermediate hosts
INTERMEDIATE HOSTS
Contamination of
food and water
Ingests cysts
in infected meat
Infection of fetus
Tachyzoites
transmitted
through placenta
Cats 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 disease
in humans and most animals .
There are two asexual forms. The first form, called
tachyzoite,( fast replicating form) can invade all types of cells and divides rapidly, leading to cell death .
The second form, called the bradyzoite, divides
slowly and forms cysts, most prominently in
muscle and brain. Tissue cysts can be ingested by a cat where they undergo sexual reproduction and oocyst formation.

12. Toxoplasma gondii – Life cycle
Oocyst
Bradyzoite
Tachyzoite

13. Transplacental Transmission of Toxoplasmosis
Occurs when primary infection occurs during pregnancy
Risk and severity vary depending on the trimester in which infection occurs
1st trimester: 15% of fetuses infected
2nd trimester: 30% of fetuses infected
3rd trimester: 60% of fetuses infected
But the earlier in pregnancy the infection occurs, the more severe the fetal infection
Transplacental 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 Hydrocephalus
Intracranial calcification
Chorioretinitis

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 women
Stillbirth - in affected pregnant women
Fetal or newborn complications of a pregnant woman with toxoplasmosis:
Congenital toxoplasmosis - passed to newborn by infected mother by cross-placental contagion.
Neonatal jaundice
Newborn brain disorders
Newborn eye disorders

17. Some pictures of symptoms of Congenital Toxoplasmosis:
Hydrocephalus

18. Congenital Toxoplasmosis:
Intracranial calcification
Chorioretinitis

19. Toxoplasmosis Disease

20. Diagnosis of Toxoplasmosis
Diagnosis of Toxoplasmosis: pregnant women
Serological diagnosis in case of
maternal (swollen lymphatic glands, fever) or
fetal symptoms (detected in ultrasound) :
Serological screening: to detect asymptomatic infections

21. Diagnosis
A)Clinical diagnosis:- Depends on history and clinical picture.
B)Laboratory diagnosis:-
1- Direct methods :-Biobsy
2-Indirect methods :-
a)Toxoplasmin skin test
b )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. DIAGNOSIS
IgG appear within 2 weeks of infection, peak in 6-8 wks, then decline over next 2 years, but detectable for life
IgM 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 to
find 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 diagnosis
Serological 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!

28. Treatment of pregnant women
Before 16th weeks' gestation
4 weeks Spiramycine [Rovamycine©]
After 16th weeks' gestation , if fetus is infected:
alternating to birth 4 weeks combination of:Pyrimethamin [Daraprim©], Sulfadiazin, Folinic Acid 4 weeks Spiramycine [Rovamycine©]
After 16th weeks' gestation, if fetus is not infected:
Spiramycine [Rovamycine©] to birth The combination of:Pyrimethamin [Daraprim©], Sulfadiazin, can pass through placenta and treat the fetus. But it is not allowed to give before about 16th weeks' gestation.

29. Treatment of prenataly infected children
Treatment of prenataly infected children with (symptomatic) disease
6 months: Combination of: Pyrimethamin [Daraprim©) Sulfadiazin Folinic Acid
6 months: alternating to the first birthday
4 weeks Spiramycine [Rovamycine©]
4 weeks Pyrimethamin [Daraprim©], Sulfadiazin, Folinic Acid .

30. Treatment of prenataly infected children with subclinical infection (no symptoms)
6 weeks: A) Combination of: Pyrimethamin [Daraprim©] Sulfadiazin Folinic Acid 6 weeks: B) Spiramycine [Rovamycine©] alternating A and B to the first birthday 4 weeks Pyrimethamin [Daraprim©], Sulfadiazin, Folinic Acid 6 weeks Spiramycine [Rovamycine©]  

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.

32. Textbook