Atypical congenital toxoplasmosis presenting with neonatal jaundice and central nervous system involvement: a case report and therapeutic challenges to limited access to first-line anti-toxoplasma medications.

BACKGROUND: Congenital toxoplasmosis (CT) is a vertically transmitted infection with a variable clinical spectrum, ranging from asymptomatic infection at birth to severe neurological and ocular sequelae. While the classic triad of hydrocephalus, intracranial calcifications, and chorioretinitis is well characterized, isolated neonatal hyperbilirubinemia as the initial presenting feature is uncommon and may delay diagnosis. We report a case of CT in a Chinese neonate who presented with jaundice and was subsequently found to have subclinical active chorioretinitis, cerebral edema, and bilateral central auditory pathway dysfunction. The case also illustrates therapeutic challenges related to the availability of first-line anti-parasitic agents.

CASE PRESENTATION: A 9-day-old term male infant was admitted for persistent jaundice. He was born at 39 + 4 weeks' gestation, with a prenatal history notable only for maternal cat exposure and treated hypothyroidism. Initial serological testing at the referring hospital revealed positive Toxoplasma gondii IgM and IgG. After transfer, two consecutive blood metagenomic next-generation sequencing (mNGS) tests detected T. gondii DNA (reads: 6 and 7). The combination of negative first-trimester maternal serology, postpartum maternal IgM/IgG positivity, neonatal IgM positivity, and repeated detection of T. gondii DNA in neonatal blood strongly supported congenital toxoplasmosis. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein, while CSF mNGS was negative, possibly reflecting low pathogen burden or compartmentalized infection. Further evaluation demonstrated bilateral active chorioretinitis on fundoscopic examination, abnormal brainstem auditory evoked potentials consistent with bilateral central auditory pathway dysfunction, and brain MRI showing cerebral edema with punctate hemorrhages. Due to initial unavailability of pyrimethamine, azithromycin followed by trimethoprim-sulfamethoxazole was administered; however, no clear improvement in CSF inflammatory indices was observed during this period. After initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid, the patient demonstrated rapid clinical improvement and radiological resolution of brain lesions on follow-up MRI, with marked improvement of chorioretinal scars.

CONCLUSIONS: Clinicians should consider congenital toxoplasmosis in neonates with unexplained jaundice, even in the absence of classic clinical manifestations. Comprehensive multi-organ evaluation, including neuroimaging, ophthalmologic examination, and auditory testing, is essential for early disease characterization. Standard pyrimethamine-sulfadiazine-folinic acid therapy may be associated with better clinical and radiological outcomes and should be used when available. Long-term multidisciplinary follow-up is necessary to monitor potential sequelae.