Toxoplasmosis (Congenital)

Congenital Toxoplasmosis

Congenital toxoplasmosis results from transplacental transmission of Toxoplasma gondii during primary maternal infection in pregnancy. 70–90% of infected neonates are asymptomatic at birth, but up to 90% develop late sequelae (chorioretinitis, neurodevelopmental delay, hearing loss) without treatment.[1-2] The classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications is rare but highly suggestive.[3]

1. History

• Maternal history is paramount: Ask about seroconversion during pregnancy, timing of infection relative to gestational age, and whether prenatal treatment was administered[4-5]
• Exposure risks: consumption of raw/undercooked meat, contact with cat feces, gardening without gloves, contaminated water[2]
• Timing of maternal infection determines severity vs. transmission rate:
• First trimester: low transmission (~10–15%) but highest severity if infected[6-7]
• Third trimester: high transmission (>60%) but lower severity[2]
• Prior maternal serostatus: infection acquired >3 months before conception carries essentially zero congenital transmission risk[8]
• Prenatal screening results (IgG/IgM), amniocentesis PCR results, prenatal ultrasound findings[5]

2. Alarm Features

• Hydrocephalus (progressive head enlargement, bulging fontanelle, sunsetting eyes)[3-4]
• Seizures at birth or in the neonatal period[1][4]
• Severe thrombocytopenia with petechiae/purpura[1]
• Severe jaundice with hemolysis and pancytopenia[9]
• Microcephaly suggesting severe early gestational infection[10]
• Signs of generalized systemic disease: hepatosplenomegaly, ascites, diffuse rash[1-2]
• Active chorioretinitis threatening the macula[3]
• CSF protein >1,000 mg/dL (indicates severe CNS involvement, warrants corticosteroids)[1]

3. Medications

Preferred neonatal treatment (12-month course)

• Pyrimethamine: loading dose 2 mg/kg/day PO × 2 days → 1 mg/kg/day × 2–6 months → 1 mg/kg 3 times weekly
• Sulfadiazine: 50 mg/kg PO twice daily
• Leucovorin (folinic acid): 10 mg PO or IM with each dose of pyrimethamine (to prevent hematologic toxicity)

Alternatives

• If pyrimethamine unavailable: TMP-SMX (age-appropriate dosing) may substitute[1][11]
• Sulfonamide-intolerant: clindamycin 5–7.5 mg/kg/dose QID with pyrimethamine + leucovorin[1]
• Azithromycin has been used in case reports with good response[9]
• Corticosteroids (prednisone 1 mg/kg/day or dexamethasone) for CSF protein >1,000 mg/dL or significant mass effect; discontinue as soon as possible[1]

Prenatal treatment

• <14 weeks gestation: spiramycin (not commercially available in the US; requires FDA assistance)[2][5]
• ≥14 weeks gestation: pyrimethamine + sulfadiazine + leucovorin[5]
• Prenatal treatment reduces infection risk (RR 0.34) and clinical manifestations (RR 0.30)[12]

Contraindications/Cautions

• Pyrimethamine is teratogenic; requires CBC monitoring at least weekly while on daily dosing[1][13]
• Warn caregivers about signs of bone marrow suppression: sore throat, pallor, purpura, glossitis[13]

4. Diet

• Not directly applicable to the neonate
• Maternal prevention is key: avoid raw/undercooked meat, unpasteurized dairy, unwashed produce[2]
• Ensure adequate maternal nutrition during breastfeeding (breastfeeding is not contraindicated in toxoplasmosis)

5. Review of Systems

• Neurologic: seizures, abnormal tone (hyper- or hypotonia), poor feeding, irritability, lethargy, abnormal head circumference trajectory[4]
• Ophthalmologic: strabismus, nystagmus, leukocoria (white pupillary reflex)[3]
• Hematologic: pallor, petechiae, bruising[1]
• GI/Hepatic: jaundice, abdominal distension, hepatosplenomegaly[1-2]
• General: fever, rash (maculopapular), failure to thrive, generalized lymphadenopathy[1]
• Auditory: sensorineural hearing loss (may present later)[4]

6. Collateral History and Family History

• Maternal serologic history: pre-pregnancy IgG status, seroconversion timing, IgG avidity results[14-15]
• Maternal treatment during pregnancy and duration[12][16]
• Prenatal ultrasound findings (ventriculomegaly, calcifications, ascites, placental thickening)[3]
• Amniocentesis PCR results if performed[5]
• Cat ownership, dietary habits, travel to endemic regions, gardening exposure[2]
• Family history is not a significant factor (not a hereditary condition), but maternal HIV status is critical as it increases risk of reactivation and severity[1]

7. Risk Factors

• Primary maternal infection during pregnancy (not reactivation in immunocompetent hosts)[2][7]
• Maternal seronegative status at conception[2]
• Geographic region: higher prevalence in France, Brazil, parts of Africa[7][12]
• Consumption of raw/undercooked meat (especially lamb, pork, venison)[2]
• Contact with cat feces or contaminated soil[2]
• Lack of prenatal screening programs[11][16]
• Maternal HIV/immunosuppression: risk of reactivation and congenital transmission[1]
• Later gestational age at infection → higher transmission rate; earlier gestational age → more severe disease[4][6]

8. Differential Diagnosis

• No signs of congenital toxoplasmosis are pathognomonic; the presentation overlaps with other TORCH infections:[3]
• Congenital CMV: most common congenital infection; periventricular calcifications (vs. diffuse/scattered in toxoplasmosis), sensorineural hearing loss, petechiae, hepatosplenomegaly
• Congenital rubella: cataracts, cardiac defects (PDA), sensorineural hearing loss, "blueberry muffin" rash
• Congenital syphilis: hepatosplenomegaly, snuffles, osteochondritis, mucocutaneous lesions, positive RPR/VDRL
• Congenital HSV: vesicular skin lesions, encephalitis, DIC, liver failure
• Congenital Zika: severe microcephaly, arthrogryposis, subcortical calcifications
• Congenital lymphocytic choriomeningitis virus (LCMV): hydrocephalus, chorioretinitis, periventricular calcifications
• Neonatal sepsis: may mimic systemic toxoplasmosis with hepatosplenomegaly, jaundice, thrombocytopenia
• Key distinguishing feature: Intracranial calcifications in toxoplasmosis are typically diffuse/scattered throughout the parenchyma, whereas CMV calcifications tend to be periventricular.[1][10]

9. Past Medical History

• Prenatal care records: frequency and results of serologic screening[11]
• Maternal treatment history (spiramycin vs. pyrimethamine-sulfadiazine, timing of initiation)[12][16]
• Prenatal imaging findings[3]
• Birth history: gestational age, birth weight, APGAR scores
• Prior pregnancies affected by toxoplasmosis (rare if immunocompetent, as prior infection confers immunity)[7]
• Maternal HIV status and CD4 count[1]

10. Physical Exam

• Head circumference: macro- or microcephaly; bulging fontanelle (hydrocephalus)[4]
• Neurologic: tone abnormalities, seizure activity, developmental reflexes, sunsetting sign[4]
• Eyes: fundoscopic exam for chorioretinitis (white retinal lesions with minimal hemorrhage), strabismus[1][3]
• Skin: maculopapular rash, petechiae, jaundice[1]
• Abdomen: hepatosplenomegaly, ascites[1-2]
• Lymph nodes: generalized lymphadenopathy[1]
• Vital signs: fever may be present in systemic disease

11. Lab Studies

Serologic diagnosis

• Toxoplasma-specific IgM (neonatal serum): positive in ~60–77% of infected neonates at birth
• Toxoplasma-specific IgA: may be more sensitive than IgM in some assays, though 20–30% of infected neonates will be missed by IgA/IgM alone[1]
• Toxoplasma-specific IgG: persistence beyond 12 months of age confirms congenital infection (maternal IgG crosses placenta and wanes by ~6–12 months)
• Compared immunological profile (CIP)/Western blot: detects neosynthesized IgG/IgM; 98% sensitivity in first 10 days of life[17]
• IgG avidity testing (maternal): low avidity suggests recent infection[14-15]

PCR

• T. gondii DNA PCR on CSF, blood (buffy coat), urine, placental tissue
• Reference laboratory testing recommended (e.g., Palo Alto Medical Foundation Toxoplasma Serology Laboratory)[15]

Additional labs

• CBC with differential: anemia, thrombocytopenia, neutropenia[1]
• LFTs, bilirubin (direct and indirect)[9]
• CSF analysis: protein, cell count, glucose, PCR[1]
• Reticulocyte count if hemolysis suspected[9]
• Monitoring on treatment: Weekly CBC while on daily pyrimethamine; at least monthly on less-than-daily dosing[1]

12. Imaging

• Head CT (non-contrast): first-line for detecting intracranial calcifications (diffuse, scattered throughout parenchyma) and hydrocephalus[1]
• Brain MRI: more sensitive for parenchymal lesions, white matter abnormalities, and basal ganglia involvement; better characterization of ventriculomegaly[1]
• Prenatal ultrasound findings that may have been noted: intracranial calcifications, ventricular dilatation, hepatic enlargement, ascites, increased placental thickness[3]
• Imaging is mandatory in all suspected cases to assess for hydrocephalus and calcifications[1][18]

13. Special Tests

• Comprehensive ophthalmologic examination (dilated fundoscopy): mandatory at diagnosis and serially throughout childhood[1][19]
• Auditory brainstem response (ABR): screen for sensorineural hearing loss[1]
• Neurodevelopmental assessment: baseline and serial evaluations[4]
• Lumbar puncture: CSF protein, cell count, T. gondii PCR[1]
• Parasite isolation: mouse inoculation or tissue culture from CSF, blood, placenta, urine (reference lab)[1]
• Amniocentesis PCR (prenatal, ≥18 weeks gestation): sensitivity ~65–90% for fetal infection[5-6]

14. ECG

• Not routinely indicated unless clinical suspicion for myocarditis/cardiomyopathy, which is a rare manifestation of disseminated toxoplasmosis[1]
• If suspected: ECG may show conduction abnormalities, ST changes, or arrhythmias; echocardiography is more informative

15. Assessment

Severity stratification

• Subclinical (majority at birth): normal exam, identified only by screening; still at high risk for late sequelae without treatment
• Mild/moderate: isolated chorioretinitis or scattered calcifications without hydrocephalus
• Severe: hydrocephalus, extensive calcifications, microcephaly, seizures, generalized systemic disease

Key prognostic factors

• Gestational age at maternal infection (earlier = more severe)
• Whether prenatal treatment was administered (4-fold lower risk of clinical features at birth with treatment)[16]
• Timing of postnatal treatment initiation (treatment within first 2 months is protective against new retinochoroidal lesions)[21]
• Parasite genotype virulence (Type I and atypical strains in South America tend to be more virulent)[4]
• Treatment of infants without substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1 year resulted in normal cognitive, neurologic, and auditory outcomes for all patients in the National Collaborative Chicago-Based Study.[20]

16. Treatment Plan

Initial stabilization

• Assess for and manage hydrocephalus (neurosurgical consultation for CSF shunting or endoscopic third ventriculostomy if symptomatic)[22]
• Manage seizures with anticonvulsants as needed[1]
• Treat severe jaundice/hemolysis (phototherapy, exchange transfusion if indicated)[9]

Pharmacologic treatment

• Pyrimethamine + sulfadiazine + leucovorin × 12 months (see dosing in Medications section above)
• Corticosteroids if CSF protein >1,000 mg/dL or significant mass effect; taper as soon as clinically feasible[1]

Monitoring during treatment

• Weekly CBC while on daily pyrimethamine; monthly on thrice-weekly dosing[1]
• Serial ophthalmologic exams[19]
• Serial head imaging to monitor hydrocephalus/calcifications
• Neurodevelopmental assessments

Surgical

• VP shunt or endoscopic third ventriculostomy for progressive hydrocephalus (~50% success with ETV in selected cases)[22]

17. Disposition

• Admit all symptomatic neonates for initial workup, treatment initiation, and monitoring
• Admit if hydrocephalus, seizures, severe jaundice, significant cytopenias, or hemodynamic instability
• Asymptomatic neonates identified by screening may be managed outpatient with close follow-up after initial workup (including LP, head imaging, ophthalmologic exam) is completed[23]
• Infectious disease consultation is recommended for all confirmed or suspected cases[1]
• Neurosurgery consultation for hydrocephalus[22]
• Ophthalmology consultation for all cases[1]

18. Follow Up / Return Precautions

Follow-up schedule

• Weekly CBC during daily pyrimethamine therapy[1]
• Ophthalmologic exams: at diagnosis, then every 3 months during the first year, then at least annually; retinochoroiditis can develop well into adulthood with peak incidences at 7 and 12 years of age[19][24]
• Audiology: at diagnosis and periodically (sensorineural hearing loss may be delayed)[4]
• Neurodevelopmental monitoring: serial assessments through childhood[20]
• Serologic follow-up: IgG levels monitored to confirm congenital infection (persistence beyond 12 months) or resolution (decline of passively transferred maternal antibody)[1]

Return precautions (counsel caregivers)

• Increasing head circumference, bulging fontanelle, vomiting, irritability, lethargy (worsening hydrocephalus)
• New seizure activity
• Pallor, petechiae, fever, sore throat (pyrimethamine-related bone marrow suppression)[13]
• Visual changes or strabismus (new chorioretinitis)
• Poor feeding, developmental regression
• Expected course: With 12 months of treatment, >72% of infants even with moderate-to-severe neurologic disease at birth achieve normal cognitive outcomes; 91% of those without substantial neurologic disease do not develop new eye lesions.[20] However, lifelong ophthalmologic surveillance is warranted given the risk of late retinochoroiditis.[19][24]

References

1. Guidelines for the Prevention and Treatment of Opportunistic Infections in Children With and Exposed to HIV. — Bill G. Kapogiannis, Franklin Yates, Wei Li, et al Office of AIDS Research Advisory Council (2025). 2025.

2. Practice Bulletin No. 151: Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy. — Committee on Practice Bulletins—Obstetrics Obstetrics and Gynecology. 2015.

3. Toxoplasmosis. — Montoya JG, Liesenfeld O. Lancet. 2004.

4. Congenital Toxoplasmosis. — Cerisola A, Francia M, Gesuele JP. Seminars in Pediatric Neurology. 2025.

5. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. — Constance Benson, John Brooks, Shireesha Dhanireddy, et al Infectious Diseases Society of America; Office of AIDS Research Advisory Council (2025). 2025.

6. Prenatal Education for Congenital Toxoplasmosis. — Di Mario S, Basevi V, Gagliotti C, et al. The Cochrane Database of Systematic Reviews. 2015.

7. A Review on the Present Advances on Studies of Toxoplasmosis in Eastern Africa. — Mose JM, Kagira JM, Kamau DM, et al. BioMed Research International. 2019.

8. Neglected Parasitic Infections: What Family Physicians Need to Know—A CDC Update. — Cantey PT, Montgomery SP, Straily A. American Family Physician. 2021.

9. One Severe Case of Congenital Toxoplasmosis in China With Good Response to Azithromycin. — Li J, Zhao J, Yang X, et al. BMC Infectious Diseases. 2021.

10. Infectious Causes of Microcephaly: Epidemiology, Pathogenesis, Diagnosis, and Management. — Devakumar D, Bamford A, Ferreira MU, et al. The Lancet. Infectious Diseases. 2018.

11. Diagnosis and Treatment of Congenital Toxoplasmosis: An Updated Overview. — Nguyen TG, Garnaud C, Brenier-Pinchart MP, Robert MG. Expert Review of Anti-Infective Therapy. 2026.

12. Treatment Protocols for Gestational and Congenital Toxoplasmosis: A Systematic Review and Meta-Analysis. — Ribeiro SK, Mariano IM, Cunha ACR, et al. Microorganisms. 2025.

13. FDA Drug Label. — Updated date: 2021-11-11. Food and Drug Administration.

14. Congenital Toxoplasmosis: An Overview of the Neurological and Ocular Manifestations. — Khan K, Khan W. Parasitology International. 2018.

15. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.

16. REIV-TOXO Project: Results From a Spanish Cohort of Congenital Toxoplasmosis (2015-2022). The Beneficial Effects of Prenatal Treatment on Clinical Outcomes of Infected Newborns. — Guarch-Ibáñez B, Carreras-Abad C, Frick MA, et al. PLoS Neglected Tropical Diseases. 2024.

17. Contribution of Serology in Congenital Toxoplasmosis Diagnosis: Results From a 10-Year French Retrospective Study. — Denis J, Lemoine J-P, L'ollivier C, et al. Journal of Clinical Microbiology. 2023.

18. Challenges in Diagnosis of Congenital Toxoplasmosis on Postimplementation of Minas Gerais Screening Program. — Carellos EVM, Vieira EMS, Vasconcelos-Santos DV, et al. The Pediatric Infectious Disease Journal. 2025.

19. Long-Term Ocular Outcomes in Congenital Toxoplasmosis Treated Perinatally. — Journé A, Garweg J, Ksiazek E, et al. Pediatrics. 2024.

20. Outcome of Treatment for Congenital Toxoplasmosis, 1981-2004: The National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. — McLeod R, Boyer K, Karrison T, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2006.

21. Ocular Outcome of Brazilian Patients With Congenital Toxoplasmosis. — Lago EG, Endres MM, Scheeren MFDC, Fiori HH. The Pediatric Infectious Disease Journal. 2021.

22. Toxoplasma Gondii Infections in Pediatric Neurosurgery. — Caceres A, Caceres-Alan A, Caceres-Alan T. Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery. 2024.

23. Neonatal Serologic Screening and Early Treatment for Congenital Toxoplasma gondii Infection. — Guerina NG, Hsu HW, Meissner HC, et al. The New England Journal of Medicine. 1994.

24. Ophthalmic Outcomes of Congenital Toxoplasmosis Followed Until Adolescence. — Wallon M, Garweg JG, Abrahamowicz M, et al. Pediatrics. 2014.