SCREENIG FOR TOXOPLASMOSIS IN SLOVENIA Mr. Sc. Tjaša Žohar Čretnik, MD Vienna, 7th of april 2015
NATIONAL LABORATORY OF HEALTH, ENVIRONMENT AND FOOD CENTRE FOR MEDICAL MICROBIOLOGY Prvomajska 1 2000 Maribor Slovenia
DIAGNOSTIC MICROBIOLOGY IN SLOVENIA 11 diagnostic laboratories (8 in NLHEF) - appointed by Ministry of health around 400 employees (1,14% of all health care employees) (218 in NLHEF) 37 specialists on microbiology 700 methods and techniques and around 2.000.000 tests performed per year 0,8 % of health care budget is spent on clinical microbiology testing 28 hospitals ant 74 primary health care centres
SEROLOGICAL TESTING FOR TOXOPLASMA INFECTION nonobligatory screening instituted in 1981 Logar J. Zdrav Vest 1981; 50:295-7. obligatory since 1995 based on estimated incidence of congenital toxoplasmosis 3/1000 live births 8 appointed laboratories (in 1998) three times during pregnancy as soon as possible -12 th week 20 24 th week 32 36 th week written interpretation of results by medical doctor, specialist on microbiology on the report
NO. OF LIVE BIRTHS 1995-2014 (383.453)
SEROPREVALENCE 52 % of seropozitive pregnant women in 1980 (unpublished data) 34% out of 21270 tested (1996-1999) Logar J at al., Scand J Infect Dis 2002; 34:201-4 24,8 % out of 47048 tested (2000-2007) Brdnik J. 2008; Graduation Thesis
SEROPREVALENCE IN CELJE REGION (32.765 PREGNANCIES)
INCREASE IN NO. OF TESTS PERFORMED (MORE THAN 40 %)
ACUTE INFECTIONS IN PREGNANCY Estimated burden of congenital toxoplasmosis for Slovenia by WHO - 1,9 CT cases per 1000 births Rotgerson T, Mastroiacovo P; Bull World Health Organ 2013;91:501-5. 6/1000 pregnant women 1989-1991 Logar J et.al. Scand. J Infect Dis 1992; 24: 105-8. 7/1000 pregnant women 1991-1995 Logar J et.al. Scand. J Infect Dis 1995; 27: 163-4. 9,4/1000 pregnant women 1996-1999 unpublished data 9,7/1000 pregnant women 2000-2007 Brdnik J Graduation Thesis 2008, University of Ljubljana
NO. OF ALL REPORTED CASES OF ACUTE INFECTIONS Year No. of reported cases Per 1000 live births?? 2008 20 0,93 2009 16 (1CT) 0,74 2010 17 0,77 2011 21 0,97 2012 17 0,79 2013 30 1,45
ACUTE INFECTIONS IN CELJE REGION From 2001 to 2014 30614 pregnant women tested 48 confirmed infections (1,6/1000 pregnancies) 33 seroconversions 15 4x rise of titre all IgM, IgA positive with low avidity of IgG 56 cases positive for IgM, IgA, low avidity of IgG and no dynamic in titre (1,9/1000 pregnancies) No cases of symptomatic congenital toxoplasmosis
UNVANTED TEST RESULTS False positive IgG result lost from further screening unrecognized infection False negative IgM result missed acute infection in early phase (delay of 3 months) False positive IgM result fear, unnecessary additional testing False negative IgG result unnecessary additional testing Screenings regarded as business opportunities everybody wants to do it!
QUESTIONS FOR LABORATORIES Which test is good enough? validation - producer 93,3-100% spcificity 77,5-99,1% sensitivity for IgM tests (by FDA) verification published articles demonstration by laboratory Are they equivalent and how to compare them? What kind of additional testing is necessary?
COMPARISON OF PARTICIPANTS IN EQA Two different testing systems (A and B) From 2002-2014 40248 scored test results analysed
test parameter IgG positive IgG negative IgM positive IgM negative A No. of results 11322 8268 2731 4028 No. of correct results 10964 8219 2694 4003 % of correct results 96,84 99,41 98,65 99,38 No. of incorrect results 45 34 20 16 % of incorrect results 0,40 0,41 0,73 0,40 No. of equivocal results 313 15 17 9 % of equivocal results 2,76 0,18 0,62 0,22 B No. of results 5668 4211 1647 2373 No. of correct results 5507 4074 1466 2305 % of correct results 97,16 96,75 89,01 97,13 No. of incorrect results 50 80 34 45 % of incorrect results 0,88 1,90 2,06 1,90 No. of equivocal results 111 57 147 23 % of equivocal results 1,96 1,35 8,93 0,97
CONSEQUENCES OF DIFFERENT PERFORMANCE 0,41 % versus 1,9 % false positive IgG results (4X) 0,40 % versus 1,9 % false positive IgM results (4x) 0,40 % versus 0,88% false negative IgG results (2x) 0,73 % versus 2,06 % false negative IgM result (3x)
ADDITIONAL TESTING TO AVOID FALSE RESULTS False positive IgG result IIF in sera with reactivity from1-15 IU/ml False negative IgM result avidity of IgG in sera with high negative IgM results (OD from 0,3 to 0,55) another IgM test if IgG is negative False positive IgM result confirmation of positive or equivocal IgM result with another test (ELISA, WB) avidity of IgG in all sera positive or equivocal for IgM False negative IgG result IIF in sera with reactivity from1-15 IU/ml All control samples tested in paralel (in the same run) IIF, IgM, IgA, WB
CONCLUSIONS Strict reporting Collection of national data Testing performed in limited number of appointed laboratories which work in close cooperation Set price