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Journal of Inherited Metabolic Disease

, Volume 33, Supplement 2, pp 241–247 | Cite as

Congenital toxoplasmosis—a report on the Danish neonatal screening programme 1999–2007

  • Dennis Röser
  • Henrik Vedel Nielsen
  • Eskild Petersen
  • Peter Saugmann-Jensen
  • Peter Bent Nørgaard-Pedersen
Newborn Screening

Abstract

Objectives

This paper reports on the national neonatal screening programme for congenital toxoplasmosis (CT) in Denmark conducted from 1999 to 2007, including background, basis for initiation of screening, methods, results, and finally reasons for the discontinuation of the screening.

Methods

A nationwide screening was conducted at Statens Serum Institut, including >98% newborns, and using filter paper eluates (Guthrie card, PKU card) obtained from newborns 5–10 days old. These were analysed for Toxoplasma gondii-specific antibodies (IgM), and if positive, then IgM (ISAGA). Confirmatory serology was performed on children and their mothers (IgM, IgG, IgA, dye test) where infection was suspected, and children with suspected or confirmed CT initiated a 3-month treatment regimen with pyrimethamine, sulfadiazine and folinic acid supplements. Selective cohorts were followed with regard to developmental and clinical outcome.

Results

A total of 100 children were diagnosed with CT in the screening period, and only 2 cases were detected outside of the screening programme. CT prevalence was 1.6 per 10,000 live-born infants. Follow-up studies showed new retinochoroidal lesions in affected children despite treatment.

Conclusion

Screening was terminated August 2007, after it became apparent that no benefit of treatment could be shown. CT was evaluated using a Danish adaptation of the Uniform Screening Panel (ACMG), showing CT as an unlikely candidate for screening today. Whereas results might be comparable with other low-endemic countries with similar strains of T. gondii, neonatal screening and treatment might offer different results in regions with either high prevalence or different strains of T. gondii.

Keywords

Pyrimethamine Neonatal Screening Prenatal Screening Congenital Toxoplasmosis Sulphadiazine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank M. Lebech, D. Schmidt and the Congenital Toxoplasmosis Screening Group for their work over the years. We thank Rune Stensvold for proofreading and helpful advice.

References

  1. ACMG (2006) Newborn screening: toward a uniform screening panel and system. Genet Med 8(Suppl 1):1S–252SGoogle Scholar
  2. Andrade GM, Vasconcelos-Santos DV, Carellos EV, Romanelli RM, Vitor RW, Carneiro AC, Januario JN (2009) Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy—an underestimated event? J Pediatr (Rio J) 86(1):85-88Google Scholar
  3. Benard A, Petersen E, Salamon R, Chene G, Gilbert R, Salmi LR (2008) Survey of European programmes for the epidemiological surveillance of congenital toxoplasmosis. Euro Surveill 13(15). http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=18834
  4. Carter AO, Gelmon SB, Wells GA, Toepell AP (1989) The effectiveness of a prenatal education programme for the prevention of congenital toxoplasmosis. Epidemiol Infect 103(3):539–545CrossRefPubMedGoogle Scholar
  5. Cook AJ, Gilbert RE, Buffolano W, Zufferey J, Petersen E, Jenum PA, Foulon W, Semprini AE, Dunn DT (2000) Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis. BMJ 321(7254):142–147CrossRefPubMedGoogle Scholar
  6. Di MS, Basevi V, Gagliotti C, Spettoli D, Gori G, D’Amico R, Magrini N (2009) Prenatal education for congenital toxoplasmosis. Cochrane Database Syst Rev (1):CD006171Google Scholar
  7. Dubey JP, Lindsay DS, Speer CA (1998) Structures ofToxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev 11(2):267–299PubMedGoogle Scholar
  8. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R (1999) Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling. Lancet 353(9167):1829–1833CrossRefPubMedGoogle Scholar
  9. Freeman K, Salt A, Prusa A, Malm G, Ferret N, Buffolano W, Schmidt D, Tan HK, Gilbert RE (2005) Association between congenital toxoplasmosis and parent-reported developmental outcomes, concerns, and impairments, in 3 year old children. BMC Pediatr 5:23CrossRefPubMedGoogle Scholar
  10. Gilbert R (2009) Treatment for congenital toxoplasmosis: finding out what works. Mem Inst Oswaldo Cruz 104(2):305–311CrossRefPubMedGoogle Scholar
  11. Gilbert R, Dezateux C (2006) Newborn screening for congenital toxoplasmosis: feasible, but benefits are not established. Arch Dis Child 91(8):629–631CrossRefPubMedGoogle Scholar
  12. Gilbert RE, Peckham CS (2002) Congenital toxoplasmosis in the United Kingdom: to screen or not to screen? J Med Screen 9(3):135–141CrossRefPubMedGoogle Scholar
  13. Gilbert RE, Freeman K, Lago EG, Bahia-Oliveira LM, Tan HK, Wallon M, Buffolano W, Stanford MR, Petersen E (2008) Ocular sequelae of congenital toxoplasmosis in Brazil compared with Europe. PLoS Negl Trop Dis 2(8):e277CrossRefPubMedGoogle Scholar
  14. Guerina NG, Hsu HW, Meissner HC, Maguire JH, Lynfield R, Stechenberg B, Abroms I, Pasternack MS, Hoff R, Eaton RB (1994) Neonatal serologic screening and early treatment for congenital toxoplasma gondii infection. The New England Regional Toxoplasma Working Group. N Engl J Med 330(26):1858–1863CrossRefPubMedGoogle Scholar
  15. Johannessen JK, Christiansen I, Schmidt DR, Petersen E, Hansen SH (2005) Simultaneous determination of pyrimethamine, sulfadiazine and N-acetyl-sulfadiazine in plasma for monitoring infants in treatment of congenital toxoplasmosis. J Pharm Biomed Anal 36(5):1093–1098CrossRefPubMedGoogle Scholar
  16. Koppe JG, Rothova A (1989) Congenital toxoplasmosis. A long-term follow-up of 20 years. Int Ophthalmol 13(6):387–390CrossRefPubMedGoogle Scholar
  17. Kur J, Holec-Gasior L, Hiszczynska-Sawicka E (2009) Current status of toxoplasmosis vaccine development. Expert Rev Vaccines 8(6):791–808CrossRefPubMedGoogle Scholar
  18. Lebech M, Andersen O, Christensen NC, Hertel J, Nielsen HE, Peitersen B, Rechnitzer C, Larsen SO, Norgaard-Pedersen B, Petersen E (1999) Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group. Lancet 353(9167):1834–1837CrossRefPubMedGoogle Scholar
  19. McAuley J, Boyer KM, Patel D, Mets M, Swisher C, Roizen N, Wolters C, Stein L, Stein M, Schey W (1994) Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chicago collaborative treatment trial. Clin Infect Dis 18(1):38–72PubMedGoogle Scholar
  20. McLeod R, Boyer K, Karrison T, Kasza K, Swisher C, Roizen N, Jalbrzikowski J, Remington J, Heydemann P, Noble AG, Mets M, Holfels E, Withers S, Latkany P, Meier P (2006) Outcome of treatment for congenital toxoplasmosis, 1981–2004: the National Collaborative Chicago-Based Congenital Toxoplasmosis Study. Clin Infect Dis 42(10):1383–1394CrossRefPubMedGoogle Scholar
  21. McLeod R, Kieffer F, Sautter M, Hosten T, Pelloux H (2009) Why prevent, diagnose and treat congenital toxoplasmosis? Mem Inst Oswaldo Cruz 104(2):320–344CrossRefPubMedGoogle Scholar
  22. Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363(9425):1965–1976CrossRefPubMedGoogle Scholar
  23. Nielsen HV, Schmidt DR, Petersen E (2005) Diagnosis of congenital toxoplasmosis by two-dimensional immunoblot differentiation of mother and child immunoglobulin g profiles. J Clin Microbiol 43(2):711–715CrossRefPubMedGoogle Scholar
  24. Peyron F (2009) When are we going to celebrate the centenary of the discovery of efficient treatment for congenital toxoplasmosis? Mem Inst Oswaldo Cruz 104(2):316–319CrossRefPubMedGoogle Scholar
  25. Remington J, Klein J, Baker C, Wilson C (2006) Infectious diseases of the fetus and newborn infant, 6th ed. Elsevier Saunders, PhiladelphiaGoogle Scholar
  26. Schmidt DR (2005) PhD Thesis: A neonatal screening programme for congenital toxoplasmosis including observations on disease development and its treatment in infants and children. Copenhagen University, Copenhagen Denmark.Google Scholar
  27. Schmidt DR, Hogh B, Andersen O, Fuchs J, Fledelius H, Petersen E (2006a) The national neonatal screening programme for congenital toxoplasmosis in Denmark: results from the initial four years, 1999-2002. Arch Dis Child 91(8):661–665CrossRefPubMedGoogle Scholar
  28. Schmidt DR, Hogh B, Andersen O, Hansen SH, Dalhoff K, Petersen E (2006b) Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine. Eur J Pediatr 165(1):19–25CrossRefPubMedGoogle Scholar
  29. Sorensen T, Spenter J, Jaliashvili I, Christiansen M, Norgaard-Pedersen B, Petersen E (2002) Automated time-resolved immunofluorometric assay for Toxoplasma gondii-specific IgM and IgA antibodies: study of more than 130,000 filter-paper blood-spot samples from newborns. Clin Chem 48(11):1981–1986PubMedGoogle Scholar
  30. Sundhedsstyrelsen (2008) Biokemisk screening for medfodt sygdom hos nyfodte - Principper, erfaringer, anbefalinger. http://www.ssi.dk/graphics/dk/diagnostik/praenatale/SST%20Biokemisk%20screening.pdf. Accessed 6 Jan 2010
  31. Thiebaut R, Leproust S, Chene G, Gilbert R (2007) Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients’ data. Lancet 369(9556):115–122CrossRefPubMedGoogle Scholar
  32. Tissot DD, Fricker-Hidalgo H, Brenier-Pinchart MP, Bost-Bru C, Ambroise-Thomas P, Pelloux H (2003) Usefulness of Western blot in serological follow-up of newborns suspected of congenital toxoplasmosis. Eur J Clin Microbiol Infect Dis 22(2):122–125Google Scholar
  33. WHO (1987) Report of the WHO consultation on public health aspects of toxoplasmosis, Hanover, Federal Republic of Germany, 6-8 October, 1987. WHO, GenevaGoogle Scholar
  34. Wilson CB, Remington JS, Stagno S, Reynolds DW (1980) Development of adverse sequelae in children born with subclinical congenital Toxoplasma infection. Pediatrics 66(5):767–774PubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Dennis Röser
    • 1
  • Henrik Vedel Nielsen
    • 1
  • Eskild Petersen
    • 2
  • Peter Saugmann-Jensen
    • 3
  • Peter Bent Nørgaard-Pedersen
    • 4
  1. 1.Department of Microbiological Surveillance and ResearchStatens Serum InstitutCopenhagenDenmark
  2. 2.Department of Infectious DiseasesAarhus University Hospital, SkejbyAarhusDenmark
  3. 3.National Board of HealthCopenhagenDenmark
  4. 4.Department of Clinical BiochemistryStatens Serum InstitutCopenhagen S.Denmark

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