Fatal Congenital Toxoplasmosis with Progressive Liver Failure and Genomic Characterization of a Novel Isolate from the United States

Congenital toxoplasmosis presents with a wide clinical spectrum, ranging from asymptomatic infection to severe disease with multi-organ failure. We report a rare fatal case of disseminated congenital toxoplasmosis in a human neonate. The infant initially had thrombocytopenia and mild hepatitis, which rapidly progressed to fulminant liver failure. Despite initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid on postnatal day 25, the infant died two days later. Autopsy revealed widespread involvement of the liver, spleen, brain, heart, lungs, urinary bladder, and skeletal muscle. To further characterize the infection, genomic sequencing of the isolate (TgHsUS2) was performed, which placed it within clade C (Haplogroup 9) and closely related to reference strains P89 and TgCatBr3. Variant analysis showed type III-like alleles in ROP18, ROP16, and GRA15. These alleles are known to modulate host immunity and may have influenced disease severity in this case. This report highlights the need for rapid recognition and targeted therapy as well as how strain genomics can inform disease mechanisms. Prevention through prenatal screening and maternal treatment during pregnancy may reduce infant mortality.