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13 Cards in this Set

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How is Toxoplasma gondii transmitted to humans?

Humans can be infected through undercooked meat, exposure to contaminated soil or water, eating soil contaminated fruits or vegetables, or exposure to infected cat feces.

What percentage of adult women in the United States have toxoplasmosis IgG antibodies, hence immunity?

Approximately 15% to 40% of adult women in the United States have toxoplasmosis antibodies IgG and thus immunity.

What is the relationship between maternal toxoplasmosis infection and fetal transmission rates and fetal sequelae?

Generally speaking the earlier the exposure the lower the vertical transmission rate. However the earlier the vertical transmission rate the more serious the sequelae.



For first trimester maternal infection with toxoplasmosis the vertical transmission rate is only 10% but 2/3 of these fetuses have severe symptoms. For example 5% of first trimester infections result in perinatal death or stillbirth.



In the second trimester the vertical transmission rate of toxoplasmosis is 25%.



In the third transmaster toxoplasmosis infection is associate of the 60% congenital infection rate. But most infections are subclinical or mild.



1st - 10%


2nd - 25%


3rd - 60%

How is acute maternal toxoplasmosis infection diagnosed?

Seroconversion demonstrated in the mother can be helpful. However IgM antibodies are present long after an acute infection. There for an acute infection of toxoplasmosis must be confirmed with avidity testing.



This means overtime the antibodies to toxoplasmosis have higher avidity. So the titers remain positive as sequentially higher levels of dilution. For example a positive titer at 1:256 dilution suggest a high avidity which is interpreted as a chronic infection.

How is fetal toxoplasmosis infection diagnosed?

Amniocentesis followed by PCR testing for toxoplasmosis DNA.

What are the treatment options for toxoplasmosis in pregnancy?

1. spiramycin


2. pyrimethamine and sulfadiazine with folinic acid

What is the classic Triad of ultrasound findings for congenital toxoplasmosis?

1. Microcephaly


2. Hydrocephalus / ventriculomegaly


3. Intracranial Microcalcifications

What is the mechanism of action for pyrimethamine?

Pyrimethamine is classified as a folic acid antagonist. It is a competitive antagonist to the enzyme dihydrofolate reductase. This interferes with the regeneration of tetrahydrofolic acid from dihydrofolate.

What is sulfadiazine?

Sulfadiazine is an antibiotic that stops the production of folate inside bacterial cells and protozoa like toxoplasmosis gondii.



It is used together with pyrimethamine to treat infection such as toxoplasmosis. It was also used together with trimethoprim to make antibiotics like Bactrim.



Sulfadiazine works by inhibiting the enzyme dihydropteroate synthetase. This enzyme is found mostly in bacteria since bacteria have to synthesize their own dihydrofolate and tetrahydrofolate.

What is folinic acid or leucovorin and why is it administered with pyrimethamine and sulfadiazine?

Leucovorin is folinic acid and is given as a rescue to limit the toxicity to both the mother and fetus secondary to the anti-folate medications.

Why is treatment of toxoplasmosis in pregnancy controversial?

Toxoplasmosis is treated with anti folates medications. Including pyrimethamine which which is a competitive antagonist of the enzyme dihydrofolate reductase. Two other medications that are also competitive antagonist of the enzyme dihydrofolate reductase include trimethoprim which is found in Bactrim and Methotrexate. Both of which are usually not used in pregnancy.



Pyrimethamine is category C in pregnancy


Sulfadiazine is category C in pregnancy


Trimethoprim is category C in pregnancy


Methotrexate is category X in pregnancy


What is spiramycin?

Spiramycin is a macrolide antibiotic and antiparacytic drug.



Spiramycin is still considered an experimental drug by the United States but can sometimes be obtained by special permission from the FDA for toxoplasmosis in the first trimester of pregnancy.

What are examples of macrolide antibiotics? Which one is contraindicated in pregnancy?

ACES


Azithromycin, category B


Clarithromycin, category C


Erythromycin, category B (erythromycin estolate - contraindicated in pregnancy secondary to hepatotoxicity)


Spiramycin, experimental



Clindamycin is not technically a macrolide. But it has the same mechanism of action as the macrolides. It is category B.



Macrolides bind the P site on the 50s subunit of the bacterial ribosome. They are considered to be bacteriostatic. The P site on the ribosome is the peptidyl tRNA site which is the position on the ribosome with a growing peptide. The A site on the ribosome is the aminoacyl-tRNA site, which is for the incoming tRNA, carrying the next amino acid.



Bonus:


What antibiotics bind the A site? The tetracyclines bind the A site by binding the 30S subunit of the ribosome. Examples include tetracycline, doxycycline, and minocycline. These are all category D.