Pyrimethamine/sulfadiazine and atovaquone impact maturation of antibodies and avidity against Toxoplasma gondii in a murine model of acute infection
Abstract number: P1875
Niewiadomski A., Alvarado Esquivel C., Schweickert B., Liesenfeld O.
Objectives: Infection with Toxoplasma gondii during pregnancy may result in congenital transmission of the parasite from the mother to the foetus. Infection is diagnosed using serological tests for IgG, IgM, and IgA antibodies. Avidity of IgG antibodies is regularly used to exclude acute infection. It has been suggested that antiparasitic treatment results in delayed maturation of IgG avidity. However, detailed studies on the effects of antiparasitic treatment on maturation of IgG avidity are lacking. We therefore investigated the maturation of antibodies and IgG avidity in a murine model of acute infection with T. gondii.
Methods: NMRI-mice were orally infected with 10 cysts (ME49) and treated with spiramycin, pyrimethamine plus sulfadiazine (pyr/sulf), azithromycin, or atovaquone (at dosages equivalent to patient dosages) from day 4 to day 10 p.i., or left untreated. Blood samples and brains were obtained at 14, 25, and 60 days (d) p.i. IgG, IgM, and IgA anti-T. gondii antibodies and IgG avidity were determined in serum by ELISA; numbers of cysts in brains were determined by immunohistochemistry.
Results: Concentrations of specific IgG, IgM, and IgA increased over time. IgG avidity also increased between d 14, 25, and 60 p.i. Treatment with pyr/sulf but not with spiramycin, azithromycin, or atovaquone significantly decreased concentrations of IgG but not IgM or IgA antibodies at 25 and 60 d p.i. (p < 0.01). This was paralleled by a significant decrease in cyst numbers in brains of mice treated with pyr/sulf but not other drugs. In contrast, atovaquone but not pyr/sulf or other drugs significantly decreased levels of IgG avidity at 60 d p.i. (p = 0.02).
Conclusion: Pyr/sulf but not other drugs currently used for the treatment of acute infection with T. gondii impacted the development of IgG antibodies against T. gondii and parasite numbers in a murine model of acute infection. Atovaquone but not pyr/sulf or other antiparasitic drugs impaired maturation of IgG antibodies. Future studies will have to investigate the impact of antiparasitic treatment on maturation of avidity in patients recently infected with T. gondii.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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