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Case Conference

Case Conference. Maria Victoria B. Pertubal , M.D. PGY1 21 September 2011. The Case. 1 week old male born to a 26 yo mother with positive prenatal Toxoplasma serology. Congenital T x plasmosis. Epidemiology. incidence of congenital infection (USA)

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Case Conference

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  1. Case Conference Maria Victoria B. Pertubal, M.D. PGY1 21 September 2011

  2. The Case • 1 week old male born to a 26 yo mother with positive prenatal Toxoplasma serology

  3. Congenital T x plasmosis

  4. Epidemiology • incidence of congenital infection (USA) • 1/1,000 to 1/8,000 live births. • Toxoplasmosis seroprevalence • USA 9% (2004) • France, Brazil, and Central America - 50-80% • higher prevalence of infection in warmer, more humid climates.

  5. Epidemiology • risk of transmitting infection to the fetus increases steeply with gestational age at seroconversion  • (Meta-analysis study on Risk of Transmission): • 15 % - 13 weeks AOG • 44 % - 26 weeks AOG • 71 % - 36 weeks AOG • 7-60% of lamb • 3-35% of pork • 0-9% of beef

  6. Historical Background • 1908 – Nicolle & Manceux Observed parasites in blood, liver and spleen of a North African rodent Ctenodactylus gondii (gundi) • 1909 – named “Toxoplasma” (bow or arc shape) • 1923 – Janku - Discovered parasite cysts on retina of an infant with hydrocephalus + seizures + ocular anomalies • 1937 - Wolf & Conan - T.gondii as cause of neonatal enceph. • 1942 – Paige, Cowen & Wolf - infection acquired congenitally • 1948– became a worldwide concern with development of precise serologic Dx procedures

  7. The Parasite: Toxoplasma gondii • An obligate intracellular coccidian protozoan • 3 forms: • Oocysts • Non-infective /unsporulated • Infective/ sporulated • Tachyzoites • Bradyzoites

  8. Life cycle within the definitive host: Cat (Felidae)

  9. http://www.cdc.gov/parasites/toxoplasmosis/biology.html

  10. Fetal transmission http://healthdefine.com/medical-advice/what-is-toxoplasmosis-toxoplasma-gondii

  11. Clinical manifestations of Toxoplasmosis infection Acquired later in life • in older immunocompetent children and adults Acquired in utero • Congenital Toxoplasmosis

  12. Clinical Manifestations in the immunocompetent host • Asymptomatic • in 80-90% • Symptomatic • Benign self-limited flu-like symptoms (from weeks to months) • any combination of fever, stiff neck, myalgia, arthralgia, maculopapular rash that spares the palms and soles, localized or generalized lymphadenopathy(20-30%),

  13. Clinical Manifestations • Other rare manifestations: • hepatomegaly, hepatitis, • reactive lymphocytosis, • meningitis, brain abscess, encephalitis, confusion, • malaise, polymyositis, • pneumonia • pericarditis, pericardial effusion, and myocarditis.

  14. Congenital Toxoplasmosis Asymptomatic/subclinical • >50% - considered normal in the perinatal period, but almost all develop ocular involvement later in life if not treated during infancy. Symptomatic disease • in the neonatal period • during first few months of life • Sequelae or relapse • (usually ocular) of undiagnosed infection later in infancy, childhood or adolescence • characteristic triad of chorioretinitis, hydrocephalus, and cerebral calcifications.

  15. Clinically apparent /symptomatic congenital toxoplasmosis • Chorioretinitis (86 %) • Abnormal cerebrospinal fluid (63 %) • Anemia (57 %) • Seizures (41 %) • Intracranial calcification (37 %) • Jaundice (43 %) • Fever (40 %) • hepatosplenomegaly (41 %) • Lymphadenopathy (31 %) • Pneumonitis (27 %) • Others: hydrocephalus (20 percent), vomiting (25 percent), eosinophilia (9 percent), rash (8 percent), and abnormal bleeding (7 percent)

  16. Congenital ToxoplasmosisTriad: Chorioretinitis Hydrocephalus Calcifications occurs in less than 10% of cases

  17. CNS • CSF abnormalities occur in at least 30% • CSF protein level of >1 g/dL is characteristic of severe CNS toxoplasmosis. • Calcifications in the brain   • Propensity for: • caudate nucleus and basal ganglia, • choroid plexus and subependyma.

  18. Figure 282-3  Head CT scans of infantswith congenital toxoplasmosis.  (Nelson Pediatrics 19th ed)A, CT scan at birth that shows areas of hypolucency, mildly dilated ventricles, and small calcifications.B, CT scan of the same child at 1 yr of age (after antimicrobial tx for 1 yr). 

  19. Eye : Chorioretinitis • most common late manifestation • incidence of new-onset retinal lesions in untreated children is almost 90 %, --risk extends into adulthood  • Relapse after treatment is common • focal necrotizing retinitis is the typical lesion • Associated findings : microphthalmia, strabismus, cataract, and nystagmus. • Complications : vision loss, retinal detachment, and neovascularization of the retina and optic nerve.

  20. (A) Severe, active retinochoroiditis. (B) Peripheral retinochoroiditis. (D) Multiple chorioretinal scars. (C) Central, healed retinochoroiditis. from Uptodate, reproduced from Centers for Disease Control and Prevention. Parasite Image Library. Available at: http://www.dpd.cdc.gov/dpdx/HTML/Image_Library.htm. Accessed sep20,2011.

  21. Evaluation • Must be done on infants born to women who are/have.. • with evidence of primary T. gondii infection during gestation  • immunosuppressed and have serologic evidence of past infection with T. gondii • Toxoplasmosis is not part of routine prenatal screening the USA • Pregnant women who experience a mononucleosis-like illness, but with a negative heterophile test, should be tested for toxoplasmosis as part of their diagnostic evaluation.

  22. Evaluation • Serology • Detection of antibodies (IgG, IgM etc..) • Serial serology is necessary to confirm or exclude congenital toxoplasmosis in asymptomatic infants • Identification of T.gondii • PCR – amniotic fluid, CSF, vitreous fluid (ocular toxoplasma), urine, peripheral blood, bronchoalveolar lavage fluid, cord blood, newborn peripheral blood, cerebrospinal fluid, or placenta • Observation of parasites /cysts • Tissue culture – innoculation in mouse

  23. Immunoflurescence Assay (IFA) A: positive reaction (tachyzoites + human Ab to Toxoplasma + FITC-labelled antihuman IgG = fluorescence.) Formalin-fixed Toxoplasmagondiitachyzoites, stained by immunofluorescence (IFA).  B: Negative IFA for antibodies to T. gondii.

  24. Unstained cyst of T. gondii. • Toxoplasma gondii cyst in brain tissue stained with hematoxylin and eosin.

  25. Interpretation of serology:Infection is confirmed if there is… • An increase in anti-Toxoplasma IgG titerduring the first year of lifeor increasing IgG titer compared with the mother’s; • the congenitally infected infant usually can synthesize Toxoplasma IgG by the third month of life if he or she is not treated; • in treated infants synthesis may be delayed until six to nine months of age • Persistence of anti-Toxoplasma IgG at one year of age • by which time transplacentally acquired maternal IgG should have disappeared)

  26. *Serology is most ideally performed or confirmed in a reference laboratory • Toxoplasmosis Serology Laboratory at the Palo Alto Medical Foundation Research Institute, California --www.pamf.org/serology; • WHO/FAO International Centre for Research and Reference on Toxoplasmosis, Staten Serum Institute, Copenhagen, Denmark; • Toxoplasma Reference Laboratory, Public Health Laboratory, Singleton Hospital, Swansea, United Kingdom). • The same serologic tests should be performed on maternal serum; maternal serum should also be obtained for differential agglutination test.

  27. Treatment • Antiparasitic therapy is indicated for infants with: • Diagnosed congenital toxoplasmosis prenatally • clinical findings compatible with congenital toxoplasmosis in the infant (chorioretinitis, intracranial calcifications, and/or hydrocephalus)with evidence of recent maternal T. gondii infection • suspected congenital toxoplasmosis who have confirmation serology or PCR performed by a *reference laboratory.

  28. Treatment regimen for Congenital toxoplasmosis • Pyrimethamine • 2 mg/kg (maximum 50 mg/dose) once daily for two days; • then 1 mg/kg (maximum 25 mg/dose) once daily for six months; • then 1 mg/kg (maximum 25 mg/dose) every other day (ie, Monday, Wednesday, and Friday) to complete one year of therapy, plus • Sulfadiazine • 100 mg/kg per day divided in two doses every day for one year, plus • Folinic acid (leucovorin) • 10 mg three times per week during and for one week after pyrimethamine therapy

  29. Glucocorticoids • (prednisone 0.5 mg twice per day) • added if cerebrospinal fluid (CSF) protein is >1 g/dL • or when active chorioretinitis threatens vision

  30. Prognosis : for the untreated infants • Poor for untreated infants with overt congenital toxoplasmosis disease at birth • Untreated infants with subclinical infection may develop chorioretinitis, seizures, and severe psychomotor retardation.

  31. Prognosis: with treatment • overall ocular prognosis usually is satisfactory • late-onset retinal lesions and relapse can occur many years after birth • may result in diminution or resolution of intracranial calcifications

  32. Prognosis • Treated infants remain at risk for developing sequelae later in life • Currently available antiparasitic drugs are active against the tachyzoite form of T. gondii but do not effectively eradicate the bradyzoite form from the CNS and eye. • recurrence of CNS and ocular disease may occur after cessation of treatment and should be monitored closely.

  33. Prevention Nelson Pediatrics 19th ed: Figure 282-1 

  34. References • Mcleod, R. Chapter 282 Toxoplasmosis. Nelson Textbook of Pediatrics May 2011 • Guerina, N. et al, Congenital toxoplasmosis: Clinical features and diagnosis. Uptodate May 2011. Accessed sep20, 2011. URL http://www.uptodate.com.elibrary.einstein.yu.edu/contents/congenital-toxoplasmosis-treatment-outcome-and-prevention?source=related_link#H4829823 • Division of Parasitic Diseases, Centers for Disease Control. DPDx Image Library. Accessed 20 sep 2011 URL http://www.cdc.gov/parasites/toxoplasmosis/biology.html • http://faculty.mwsu.edu/nursing/betty.bowles/toxoplasmosis.pdf

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