toxoplasmosi: epidemiologia, prevenzione e...

EPIDEMIOLOGIA PREVENZIONE E DIAGNOSI

Meroni V

Dipartimento Medicina Interna e Terapia Medica Universitagrave di Pavia SC Microbiologia e Virologia Fondazione IRCCS Policlinico San Matteo Pavia

SEPSI E INFEZIONI IN GRAVIDANZA BOLOGNA

17-18 ottobre 2014

Toxoplasmosi

Toxoplasma gondii bull The most successful parasite bull worldwide distribution bull capable to infect all warm-blooded animals bull highly transmissible bull frac14 of the human population is chronically infected

Low prevalence (10 -30) North America nel Suth East Asia North

Europe Sahelian country of Africa

Moderate prevalence (30-50 ) Central and Southern Europe

High prevalence (gt50 ) Latin America Tropical African countries

Robert Gangeux F Darde ML Clin Micr Rew 2012

Anti-Toxoplasma antibodies in 3047 pregnant women ( 2005-2007)

Anti-Toxoplasma antibodies

Italian women (2465)

Foreign women

(609)

P

Total women (3074)

IgG neg IgM neg

806

650

lt001

775

IgG POS IgM neg

177

332

lt001

208

IgM POS (or border line)

17

18

NS

17

De Paschale et al Microbiologia medica 2008

Anti Toxoplasma gondii antibodies in 1584 solid organ donors and recipients in

Pavia (1997-2007)

540 Donors 285 (53)seropositive

8 (15) IgM positive

1084 Recipients 611 (56 ) seropositive

Photo Luc Viatour

THE PARASITE

THE HOST

bull Inoculum +++

bull Infective stage (cysts vs oocysts)

bull Genetic background

Toxoplasmosis involves parasite and host factors

bull Interviews with a standard questionnaire

bull Europe Naples Lausanne Copenhagen Oslo Brussels and Milan

bull Main risk factor of infection with T gondii = undercooked meat (+++cyst) in all centers

bull The type of meat varies among countries

bull The authors were not able to explain 14-49 of the risk for T gondii infection depending on the center

Clin Infect Dis2009 Sep 1549(6)878-84

BMJ 2000 Jul 15321(7254)142-7

bull Questionnaire bull Contact with soil and cats bull Low educational level bull Home-made water ice bull Residence in rural areas bull Vegetables washed with

untreated water

bull Main risk factor = via oocysts in Brazil

Rev Inst Med Trop Sao Paulo 2011 Jul-Aug53(4)185-91

Am J Trop Med Hyg 2010 Sep83(3)528-33

Rev Soc Bras Med Trop 2005 Mar-Apr38(2)173-7


Low genetic diversity of T gondii strains in Europe and North America

3 major genotypes

type I 19

type II 54

type III 27

Strains from Europe in 2013 (+++ France) bull Type II

bull 99 of strains from wild and domestic animals bull 94 in congenital toxoplasmosis

bull Type III lt5 no type I bull Atypical strains= imported

Int J Parasitol 2010 Feb40(2)193-200

J Infect Dis 2002 Sep 1186(5)684-9

Strains from South America (+++ Brazil) bull almost exclusively from animals bull genetically different from type I II and III strains bull high genetic diversity countless diverse genotypes bull = atypical strains

Ocular lesions in congenital toxoplasmosis in Brazil are bull more frequent bull more recurrent bull more multiple bull larger bull more likely to impair vision than in Europe

Europe

Brazil

years

children without retinochoroiditis

Cohort of Congenital toxoplasmosis Brazil (30) Vs Europe (281)

PLoS Negl Trop Dis 2008 Aug 132(8)e277

laquo We suggest that the increased frequency and severity of ocular disease in Brazil compared with Europe is due to exposure to more virulent strains of Tgondii in Brazil raquo

Clinical case 2

- Strain genotyping - atypical strain - genotype close to 1 strain from Uruguay and 1 strain from

Nigeriahellip

- Imported food linked to the infection - raw horsemeat consumption in pregnancy (May and June) - origin of the horsemeat unknown

J Infect Dis 2009 Jan 15199(2)280-5

Virulence in human Host factor (immune status)

bull Type II chronic infection in healthy adults

bull Life threatening in immunocompromised

Brussels january 2014 13

Virulence in human Congenital toxoplasmosis

bull Age of gestation at maternal infection

Prevention of Congenital toxoplasmosis

PRIMARY Prevention of infection in pregnancy (hygienic prophilact measures )

SECONDARY Prevention of vertical trasmission and severity of fetal damages reduction ( prenatal diagnosis therapy)

TERTIARY Sequelae reduction (early diagnosis and therapy in newborns)

Decrease in severity and incidence of congenital toxoplasmodsis

16

ldquoLo screening prenatale della toxoplasmosi e raccomandato e consiste in una sierologia al primo controllo prenatale ripetuta ogni 4-6 settimane se il primo esame risulta negativo fino al termine della gravidanza Le donne devono essere informate delle misure igieniche che possono evitare lrsquoinfezione in gravidanzardquo La sua esecuzione in epoca preconcezionale e durante la gravidanza ( preferibilmente entro le prime 13 settimane di gestazione e ogni 30-40 giorni in caso di sieronegativitagrave ) egrave esentata dal pagamento del ticket ai sensi del DPR 245 del 10091998

Italian multidisciplinary document on diagnosis therapy and follow-up of toxoplasmosis in pregnancy and in newborn by 6 scientific societies

(AMCLI SIGO SIMaST SIMIT SINSIP) wwwamcliit

Serological screening

Diagnosis of Toxoplasmosis in pregnancy

Positive

Hygienic prophylactic measures Monthly control

No seroconversion seroconversion

IgG- IgM+

Previous Immunity

Serology one month later Keep the report for further

pregnancies

ACUTE INFECTION

No Immunity Counselling for further pregnancies

WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+

Low Intermediate IgG Avidity

High IgG Avidity

One month later no therapy

IgG- IgM-

Negative

In the first trimester

IgG+ IgM-

Norme igienico alimentari per la gestante recettiva alla toxoplasmosi

- cuocere sempre molto bene le carni prima del consumo - evitare il consumo di carni crude o poco cotte salumi crudi frutti mare crudi latte non pastorizzato uova crude - lavare accuratamente frutta e verdure prima del consumo - lavare sempre le mani prima di mangiare e dopo aver toccato carni crude frutta e verdure non lavate terra o altri materiali potenzialmente contaminati con le feci del gatto - pulire accuratamente le superfici della cucina e gli utensili venuti a contatto con carni crude frutta e verdure non lavate - usare sempre guanti di gomma in tutte le attivitagrave che possono comportare il contatto con materiali potenzialmente contaminati con le feci del gatto (giardinaggio orticoltura pulizia lettiera del gatto ecc) - evitare il contatto con il gatto e soprattutto con le sue feci in caso di presenza di un gatto in casa adottare le seguenti precauzioni alimentare lrsquoanimale con cibi cotti o in scatola evitando che esca di casa affidare ad altri la pulizia della sua cassetta facendo sostituire frequentemente (meglio se quotidianamente) la lettiera e igienizzando il contenitore per almeno 5rsquo con acqua bollente - evitare viaggi al di fuori dellrsquoEuropa e del Nord America - eliminare dalla propria abitazione veicoli animali (mosche scarafaggi ecc)



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Antibodies kinetics in early treated pregnant woman

Antibodies kinetics in treated pregnant woman

TEST 02112010 10112010 30112010 23122010 04012011

IgG CLIA NEG NEG 8 NEG 25

IgG ELFA NEG NEG ND 4 24

IgM CLIA POS POS POS POS POS

IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150

WB IgGIgM NEGPOS POSPOS POSPOS

IgG AVIDITY 0114

Spyramicin 1011 till 1512 2010

30 3 3

3 1

45 40

LDBIOTOXO II - (immunoblot) - ready to use - standardized(60rsquo- 60rsquo- 30rsquo) - positive control For IgG included

5 specific band 30 ndash 31 ndash 33 ndash 40 ndash 45 kDa

IgG positive 3 specific bands IgM positive 2 specific bands including 30 kDa band

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion

41 IgG-IgM+ spiramycin treated

pregnant women



Positive

Hygienc profilactic measures Monthly control


IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I

Treatment No Treatment

p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002

Maturazione dellrsquo Indice di Aviditagrave in 28 gravide trattate (122campioni) e in 16 linfoadeniti non trattate (51 campioni)

Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47

7 057 00485 72 Kappa evaluation lt0 no correlation 041-060 moderate 000-02 0 slight 061-080 good 021-040 fair 081-100 very goo

VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS

bull Great individual variability slow maturation persistence of intermediate avidity

bull Test characteristics and limits

bull Therapy effects

bull In the diagnosis of toxoplasmosis the IgG avidity test must still be considered

as an exclusion test High avidity Index clearly excludes infections in the previous

3- 4 months but low or intermediate avidity index can persist longer than expected

Normal US

Acute infection

gt 23a wks

Negative (spiramycin)

Positive

TOP

At delivery mother-newborn blood samples

IgG IgMIgA IgG IgM WB Immunological tests Clinical examination

Abnormal US

Spiramycin Ultrasound controls

Pirimethamine + sulfadiazine

Prenatal diagnosis PRC on AF gt18wks

4-6weeks after seroconversion

Diagnosis of toxoplasmosis Italian Consensus April 2012

Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098

L Thalib et al BJOG May 2005

Performance of state-of-art Toxoplasmosis PCR on amniotic fluid

Wallon et al Obstet Gynecol April 2010 - N=377

No false + Rare false -

conception 1er trimester 2eme trimester

Fetal loss

Sub cinical infection

5

40

80

Probability of congenital infection ( ) and severity of cinical signs ( ) According to gestational age at maternal seroconversion

delivery


36

Congenital toxoplasmosis

Clinical presentation

Severe malformations

Sub clinical forms

Late onset of ocular lesions

Brussels january 2014

At birth

bull Is the new born contaminated

Yes if


Yes if PCR on amiotic fluid was positive

Extremely rare usually detected by Ultra sound

38

Is he infected

Sensitivity asymp76 Specificity ~ 997

depends on age of pregnancy at maternal infection

bull Yes if IgM or IgA in peripheral blood

Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant

Do not stop folow-up before a negative serology

bull Post natal serological trough

40

The only way to rule out a congenital infection

Negative serology within the first year

Regular blood sampling

-painful

- not well accepted by parents


41 Brussels january 2014

VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G

AxSYM IgGOD salivary IgG


Mother

Newborn

9 10 IgG 72 54 IgM NEG NEG

IgM ISAGA 12+ NEG IgA 100 NEG

Isolamento NEG

IgG

IgM

IgG IgM WB Uninfected newborn

Mother Newborn

Mother

Day of Birth

1 Month

IgG IgM WB Infected newborn

17 18 IgG NEG NEG 38 IgM NEG NEG 18

IgM ISAGA NEG NEG 12+ IgA NEG NEG NEG

madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800

IgM ISAGA 12+ 12+ IgA gt 400 200

Avidity 0065

IgG IgM

IgG IgM WB at birth Infected newborn

IgG-IgM WESTERN BLOT

POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)

IgM ISAGA + IgA ELISA

POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224

IGRA TEST (QuantiFERON Cellestisreg ( ADA )

1 ml heparinized blood

Spin 10 min

Replace plasma with the same

amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag

24 hours 37degC + CO₂

Raccogliere il surnatante di ogni pozzetto

Keep plasma frozen -80deg until γ-IFN determination

by ELISA

MIT

MIT

Sensitivity Specificity Cut-Off

Sensitivity S 8158 (IC 95) R 93 (IC95)

SPECIFICITY S 8348 (IC 95) R 897 (IC95)

CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076

132 newborns from january to december 2011

Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Toxoplasma gondii bull The most successful parasite bull worldwide distribution bull capable to infect all warm-blooded animals bull highly transmissible bull frac14 of the human population is chronically infected

Low prevalence (10 -30) North America nel Suth East Asia North

Europe Sahelian country of Africa

Moderate prevalence (30-50 ) Central and Southern Europe

High prevalence (gt50 ) Latin America Tropical African countries

Robert Gangeux F Darde ML Clin Micr Rew 2012




Foreign women

(609)

P

Total women (3074)

IgG neg IgM neg

806

650

lt001

775

IgG POS IgM neg

177

332

lt001

208


17

18

NS

17



Pavia (1997-2007)


8 (15) IgM positive


Photo Luc Viatour

THE PARASITE

THE HOST

bull Inoculum +++










BMJ 2000 Jul 15321(7254)142-7


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women




Foreign women

(609)

P

Total women (3074)

IgG neg IgM neg

806

650

lt001

775

IgG POS IgM neg

177

332

lt001

208


17

18

NS

17



Pavia (1997-2007)


8 (15) IgM positive


Photo Luc Viatour

THE PARASITE

THE HOST

bull Inoculum +++










BMJ 2000 Jul 15321(7254)142-7


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


Pavia (1997-2007)


8 (15) IgM positive


Photo Luc Viatour

THE PARASITE

THE HOST

bull Inoculum +++










BMJ 2000 Jul 15321(7254)142-7


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Photo Luc Viatour

THE PARASITE

THE HOST

bull Inoculum +++










BMJ 2000 Jul 15321(7254)142-7


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women







BMJ 2000 Jul 15321(7254)142-7


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


untreated water







3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


3 major genotypes

type I 19

type II 54

type III 27





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women





J Infect Dis 2002 Sep 1186(5)684-9



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women



Europe

Brazil

years





Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Clinical case 2


Nigeriahellip


J Infect Dis 2009 Jan 15199(2)280-5












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women












16






Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women





Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women



TEST 02112010 10112010 30112010 23122010 04012011




IgM ISAGA 12+ 12+ 12+ 12+ 12+

IgA ELISA 200 250 200 150 150


IgG AVIDITY 0114


30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

30 3 3

3 1

45 40




10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women



Positive



IgG- IgM+

Previous Immunity


pregnancies

ACUTE INFECTION


WB IgGIgM IgG Neg

WB IgGIgM IgG Pos

IgG+ IgM+


High IgG Avidity


IgG- IgM-

Negative


IgG+ IgM-

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Fig 1 a

25

35

45

55

65

75

0 1 2 3 4time

log U

I


p lt 0001

Fig 1 b

25

35

45

55

65

75

85

95

0 1 2 3 4time

log U

I

p = 0026

Fig 1 c

-25

-2

-15

-1

-05

0

0 1 2 3 4time

log A

I

p = 0049

Fig 1 d

-45

-35

-25

-15

-05

0 1 2 3 4time

log A

I

p = 0002


Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Cohenrsquos Kappa

AVIDITY

TEST

k SE agreement

1 089 00468 93

2 055 00481 70

3 057 00553 72

4 051 00509 68

5 058 00489 73

6 020 00355 47


VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

VIDASy = 00208x + 00511

Rsup2 = 06619

DIASORINy = 00328x + 01087

Rsup2 = 07557

000

010

020

030

040

050

060

070

080

0 2 4 6 8 10 12 14 16

total

avi

dit

y in

de

x

months

CLIA

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

CONCLUSIONS







Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Normal US

Acute infection

gt 23a wks


Positive

TOP



Abnormal US






Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Seroconversion

Trimester

Ndeg CT+

PCR

CT-

PCR

Sensibility

Specificity

+ - + -

I 357 3 6 1 347 033 099

II 200 37 9 5 149 080 098

III 36 17 8 1 10 068 091

Tot 593 57 23 7 506 071 098






Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women





Fetal loss


5

40

80


delivery


36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

36




Sub clinical forms



At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

At birth


Yes if




38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

38

Is he infected




Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Maternal antibodies

Non infected infant

Infected infant

Birth 1 year

Infected infant



40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

40




-painful




VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


VAL Pia Toxo -

0

20

40

60

80

1 2 3 4 5 6 7 8 9 10 11 12

Age in month

Ax

SY

M I

gG

0

05

1

15

2

25

OD

Sa

liv

ary

Ig

G



Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Mother

Newborn



Isolamento NEG

IgG

IgM


Mother Newborn

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

Mother

Day of Birth

1 Month




madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

madre

figlio alla

nascita

5 6 IgG gt 300 gt300 IgM 100 800


Avidity 0065

IgG IgM



POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


POS NEG TOT

POS 38 6 44

NEG 2 178 180

TOT 40 184 224

Sens 750 (IC 95 588-873) Spec 989 (IC 95 961-993)

Sens 950 (IC 95 831-994) Spec 967 (IC 95 930-988)


POS NEG TOT

POS 30 2 32

NEG 10 182 192

TOT 40 184 224



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women



Spin 10 min


amount of RPMI

PLASMAFOR SEROLOGY

Ag NIL

NIL Ag




by ELISA

MIT

MIT




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women




CUT OFF S 0151 (IC 95) R 0156 (IC95)

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Se

ns

itiv

ity

cmi_s_ag

cmi_r_ag

P=0076


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women


Newborn IgMIgA POS

IgMIgA NEG

WB IgGIgM POS

WB IgGIgM NEG

IGRA POS

IGRA NEG

INFECTED (10) 4 6 9 1 10 0

NOT INFECTED (122) 0 122 0 122 0 65

TESTED 132 132 75

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

10 IgM ISAGA

NEG

IgG WB

NEG

IgM WB

NEG

IFN-γ

NEG

No seroconversion

14 IgM ISAGA POS

IgG WB NEG

IgM WB NEG

IFN-γ

NEG

No seroconversion

13 IgM ISAGA POS

IgG WB POS

IgM WB POS

IFN-γ

POS

Seroconversion

4 IgM ISAGA POS

IgG WB

NEG

IgM WB POS

IFN-γ

NEG

No seroconversion


pregnant women

toxoplasmosi: epidemiologia, prevenzione e...

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