Transcript CHAGAS DISEASE Overwiev Diagnosis Proposals for WHO Ref.Preparation Alejandro O. Luquetti Laboratório de Pesquisa em Doença de Chagas Hospital das Clínicas e Instituto de Patologia Tropical e Saúde.

CHAGAS DISEASE
Overwiev
Diagnosis
Proposals for WHO Ref.Preparation
Alejandro O. Luquetti
Laboratório de Pesquisa em Doença de
Chagas
Hospital das Clínicas e Instituto de
Patologia Tropical e Saúde Pública,
Universidade Federal de Goiás
Brasil
DIAGNOSIS OF CHAGAS DISEASE
LABORATORIAL DIAGNOSIS
-ONLY TWO PHASES RECOGNIZED
-ACUTE
-Vectorial, Blood, Organ,
-Congenital, Oral,
- Accidental, Reactivation
-CHRONIC -Cardiac form, Indetermined
-Digestive form, associated
-BOTH
VERY
DIFFERENT,
INCLUDING
LABORATORY TESTS EMPLOYED
DIAGNOSIS OF CHAGAS DISEASE
DIAGNOSIS (Acute and chronic phase)
A)EPIDEMIOLOGY
B)CLINICAL FINDINGS
C)LABORATORY TESTS
-All should fit
DIAGNOSIS OF CHAGAS DISEASE
LABORATORIAL DIAGNOSIS OF THE
CRHONIC PHASE
- Antibodies anti-T.cruzi present in > 98%
- Parasites present in no more than 50%,
even with PCR
- The parasitemia is usually low or absent,
inconstant, variable, erratic, and even if there, not
necessarily present at the sample (# from Ab)
- Solutions versus suspensions
DIAGNOSIS OF CHAGAS DISEASE
SEROLOGICAL DIAGNOSIS
- Presence of Ab in constant concentration in a given
individual
- Conventional tests (ELISA, IIF, IHA) in use since 1975
- Great cumulated experience in all endemic countries
- Performance depends of good quality kits and good
Laboratory practice
- Most with no purified antigen
- Problems (few) of specificity mainly with leishmaniosis
SEROLOGY IN NON-TREATED CHAGASIC PATIENTS
FOLLOW UP OF CHRONIC PHASE, CARDIAC FORM, NON TREATED PATIENT
MJS, female, 32 sera collected during 23 years
Date
Age
Ye
ELISA
IFI
HAI
BIO
FIO
WIE
IgM
RR
150878
23
0
2.4
640
32
3.3
3.0
8.2
<5
P
181082
27
4
3.1
1280
32
5.6
2.9
7.1
090596
41
17
3.6
1280
32
140797
42
19
2.6
1280
16
7.0
4.4
7.5
101297
42
19
2.5
2560
32
8.0
4.6
8.3
P
231098
43
20
2.2
1280
32
7.9
5.0
8.5
P
080499
44
20
2.5
2560
32
5.7
3.7
7.0
P
221199
44
21
2.6
1280
16
8.2
5.3
7.8
P
280600
45
21
2.5
2560
64
8.1
5.6
7.4
P
030401
46
22
3.1
2560
32
8.4
5.1
7.3
P
020102
46
23
2.9
2560
32
6.4
4.3
7.5
P
P
P
<5
P
SEROLOGY IN NON-TREATED CHAGASIC PATIENTS
FOLLOW UP OF CHRONIC PHASE, CARDIAC FORM, NON TREATED PATIENT
ICD, female, 32 sera collected during 13 years
Date
Age
Ye
ELISA
IFI
HAI
BIO
FIO
WIE
IgM
RR
181088
55
0
3.5
5120
256
7.6
8.0
6.9
40
P
040797
64
9
5.9
5120
512
8.2
5.2
20
P
040897
64
9
3.4
2560
512
8.4
4.5
80
P
030997
64
9
3.9
2560
256
8.3
7.3
160
P
090298
64
9
4.7
5120
512
8.5
7.4
80
P
170398
64
9
3.4
5120
256
8.1
7.5
40
P
241198
65
10
5.5
5120
512
9.9
6.2
7.2
20
P
221199
66
11
6.5
9999
1024
10.4
5.1
7.9
160
P
220500
66
11
4.3
5120
1024
8.8
3.9
7.3
80
P
070601
67
12
7.1
5120
256
5
P
141101
68
13
6.5
5120
512
160
P
10.9
7.5
6.6
SEROLOGICAL DIAGNOSIS OF T. cruzi INFECTION
THE QUESTION OF T. cruzi I and II & SEROLOGY
-As known:
T. cruzi I: homogeneous, north Amazonas river, Rhodn.
isolated humans and silvatic, didelphis, palm
trees, also sylvatic below Amazonas, some humans
double infection, only appears on
immunosupression or tissues, easy treatment
T. cruzi II:b: homogeneous, humans east Brazil,
associated megaesophagus, low congenital(<1%),
severe cardiopathy, difficult treatm. Years Neg.
a: silvatic, armadillo, soil(Z3), P.genic.
c: hybrid?
d & e: hybrids: south BR, AR, UR, PY, BO,
CH, easy response treatment, incl.Nf
congenital 5%, megacolon & card.
Development of the WHO International Reference
T.cruzi Panel: CANDIDATE MATERIALS:
Linajes filogenéticos de
Trypanosoma cruzi
Plasma units anti-T. cruzi positive for
ELISA, HAI, IFI and RIPA/Western Blot
from North country (e.g. Colombia, Mexico).
Plasma units anti-T. cruzi positive for
ELISA, HAI, IFI and RIPA/Western Blot
from South country (e.g. Bolivia, Brasil).


TCI
(courtesy Dr. G. Schmuñis)
I
 T.T. cruzi
IIa
 T. cruzi
IIb
 T. cruzi
IIc
 T. cruzi
IId
 T. cruzi
 cruzi IIe



 






 






 
TCII
Adaptado de Souto et al. 1996;
Fernandes et al. 1998; Brisse et al.
2000, 2004.
SEROLOGICAL DIAGNOSIS OF T. cruzi INFECTION
THE QUESTION OF T.cruzi I & II AND
SEROLOGY
-A: T. cruzi II and reagents made from T.
cruzi II: ok
-B: T. cruzi II and reagents made from T.c I
not extensively tested
Our experience (IFI, ELISA) strain
Queretaro: similar results (?)
-C: T.cruzi I and reagents made from T.cI: ok
(MX, CO)
-D: T.cruzi I and reagents made from T.cII:
some (MX, HN, CO, VE) ok
other (MX, CO) low reactivity some sera
Our experience: ok (MX, HN, CO, VZ,)
SEROLOGICAL DIAGNOSIS OF T. cruzi INFECTION
DIAGNOSIS IN EACH SITUATION
1)DIAGNOSIS OF A PATIENT
- Send by physician, for clarify etiology
- Select tests with higher specificity
- Avoid false positive, psychological and/or legal consequences
- Use two tests of different principles, conventional or one
conventional and the other rapid, or 1 ELISA crude +
ELISA recomb.
- Valorize titers
- If both positive, at higher titers, result could be signed
CHAGAS DISEASE
DIAGNOSIS OF INFECTION BY T. cruzi IN DIFFERENT
CONTEXTS
2) DONOR EXCLUSION
- Blood bank: need to offer a good quality product
- Use of kits with high sensitivity
- Avoid false-negative, legal consequences
- Use of two tests of different principle, convencional
one should be ELISA + IIF or IHA or rapid test
- Use one test, ELISA, only if a proper external
quality control exist
- If both NEGATIVE, blood may be used
LABORATOY DIAGNOSIS OF T. cruzi INFECTION
• RELIABLE RESULTS IN SEROLOGY
– Matherials: approved kit, retested for lot at the lab(internal
panel with low positives and high negatives
• Good laboratory practices: temperatures, pH, etc.
• POP : description of each procedure, in detail
– Methods: Programs of technical training (Telelab)
– Quality: Lab ought to participate in an External Quality
Control Programme, provided that:
• This programm send at least 2 panels/year
• The Lab should be approved
LABORATOY DIAGNOSIS OF T. cruzi INFECTION
• PROGRAMS of EXTERNAL QUALITY
CONTROL
– Initial difficulty to mount serum panels
(AR/CH/BR/PY) Meeting OPS-BH 1994)
– Difficult to obtain panels in non endemic countries
– Initiative of OPS/PANEL São Paulo (BR) 1995
– Programm operative in >18 countries
– Priority in reccommendations of South Cone (1999)
– Programms of Hemotherapy Societies (AR, BR)
– Programm of MPH, BR, COSAH>ANVISA (2001)
LABORATOY DIAGNOSIS OF T. cruzi INFECTION
• CONTROL QUALITY PROGRAM OF THE MINISTRY
OF HEALTH, BR FOR EXTERNAL CONTROL IN
BLOOD BANKS
–
–
–
–
–
–
–
–
–
Joint venture National Agency of Sanitary Surveill./Fiocruz
Both belong to Ministery of Health, coordination, execution
Technical Committee, 1 by area (syphilis, HIV, etc)
Several meetings/year, evaluation of results by marker
Three panels/year (6x3) – by post
Started on 2000, processed 2.718 plasma bags (2005)
From 2001 to 2008, 19 evaluations, of 135 services (90% public)
Increase in results, from 3,6 % to 0,9% discordances.)
Indirectly detected problems with different lots of used kits
LABORATOY DIAGNOSIS OF T. cruzi INFECTION
• EVALUATION OF ELISA KITS AVAILABLE IN BRAZIL
– Study performed by Lab Coordination, Min.Health
– Bought all certified kits available in Brazil (n=12)
– Selection of 152 sera (half negative)
– Blind tests by 4 labs: MG, PE, MS, GO
– Kappa index of 0,71 to 0,98. Sensitivity 0,97 a 1,0
– 6 kits sensitivity = 1,0. 5 kits = 0,99. 1 kit =0,97.
– Trades: Adaltis, Bioma, Biomerieux, Bioschil, Biozima,
– Ebram, Hemagen, Omega, REM, Wama, Wiener
– This study allows to exclude some trades, based on
published data (www.
CHAGAS DISEASE
DIAGNOSIS OF INFECTION BY T. cruzi IEIN EACH SITUATION
3)DIAGNOSIS OF CONGENITAL TRANSMISSION
- Send by pediatritian, to exclude transmission from the mother
- Reassure that mother is really infected: serology previously or,
serology of blood from umbilical cord: if negative, no transm.
- Look for parasites in the new-born (micro-hematocrit)
- Positive serological tests, only indicate maternal transference
- IgM (IIF not recomended). Anti-SAPA not available
- Better advise physician for new sample at 6-8 months:
- If IgG present, transmission is proved and child ought to be
treated.
SITUAÇÃO ATUAL DA DOENÇA DE CHAGAS
SEROLOGIA EN LACTANTES DE MADRES INFECTADAS
-RESULTADOS OBTENIDOS EN 56 LACTANTES
- Suero del primer mes: títulos muy elevados, similares a los de la
madre: (n=17)
IFI 1.280 Elisa: 2,6 HAI 256 PaGIA pos
- Suero del segundo mes: IFI 320 Elisa: 1,5 HAI 16 PaGIA variab
- Suero del tercer mes: IFI 80 Elisa: 1,2 HAI 8 PaGIA variab
- Suero del cuarto mes: IFI 40 Elisa: 0,6 HAI 4 PaGIA neg
- Suero del 6o.mes(n=13):IFI 10 a 40 Elisa: 0,6 HAI <4 PaGia neg
- Suero del 7o. mes(n=9): IFI <10 Elisa 0,4 HAI <2 PaGIA neg
- Suero del 8o. mes(n=8): IFI<10 Elisa 0,4 HAI<2 PaGIA negativo
CHAGAS DISEASE
DIAGNOSIS OF INFECTION BY T. cruzi IN EACH CONTEXT
4) FOLLOW UP OF A SPECIFICALLY TREATED
- Send by physician, looking for cure
- Cure is possible in all newborns, 60% of acute phase and
children and up to 25% of adults, after benznidazol x 60 days
- Cure criteria is abscence of antibodies, formerly present
- Time to attain: months in congenital, years in acute/children
and decades in adults
- For these, need to preserve previous sera with glicerol
- To procede in parallel com os soros anteriores e o atual
SITUAÇÃO ATUAL DA DOENÇA DE CHAGAS
DIAGNÓSTICO DA INFECÇÃO PELO T. cruzi EM CADA SITUAÇÃO
4) SEGUIMENTO DE INFECTADO TRATADO 50 dias de inicio sintomas
- Exemplos de viragem de títulos: Fase aguda. IgM 1o. Soro 640. Subclasses <10
Data
Idade
ELISA
IFI
HAI
HAI+2ME
ELISA
Biolab
ELISA
Fiocruz
270481
10
1.4
160
64
16
1.2
6.2
110581
10
1.7
1280
32
-
3.5
4.2
070781
10
1.0
<10
16
<8
1.6
4.3
280482
11
1.2
<10
4
-
1.1
2.3
190686
15
0.5
<10
<2
-
0.5
0.6
100293
21
0.8
<10
16
<8
0.1
0.8
070596
25
0.9
40
16
4
0.4
0.6
SITUAÇÃO ATUAL DA DOENÇA DE CHAGAS
DIAGNÓSTICO DA INFECÇÃO PELO T. cruzi EM CADA
SITUAÇÃO
4) SEGUIMENTO DE INFECTADO TRATADO
- Exemplos de viragem de títulos: Fase aguda VRSA
Data
Idade
ELISA
IFI
HAI
HAI+2ME
ELISA
Biolab
ELISA
Fiocruz
280683
36
0.7
10
<4
-
1.1
0.8
010783
36
1.5
80
8
<8
0.6
1.2
150983
36
0.7
160
8
<8
1.2
-
110785
38
2.2
640
64
16
5.1
-
210786
39
2.5
160
64
32
3.4
-
140788
41
3.1
640
32
-
4.7
5.1
090903
56
3.3
2560
64
-
8.5
6.4
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
WHO INTERNATIONAL BIOLOGICAL REFERENCE PREPARATION
- Biological standard: measure concentration of substance that cannot be
characterised by chemical and physical methods
-International standard: preparation to which an International Unit has
been assigned
- WHO holds a number of reference sera for several diseases (syphilis,
hepatitis, etc.). Also, vaccines, toxoids. Chagas is not included.
-Expert Committee on Biological Standardization meets once a year.
Each preparation is analised, as well as candidates and substitutions
need to be aproved.
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
WHO INTERNATIONAL BIOLOGICAL REFERENCE PREPARATION
- The Expert Committee on Biological Standardization, note the absence of a
Biological standard (serum) on Chagas disease (Dr. Padilla).
- A WHO Consultation on International Biological reference preparations
for Chagas diagnostic tests was launched.
- This meeting was held previously to the annual meeting, from 2 to 3 July
2007, in Geneve, with 33 participants (half specialists) and 4 industries.
- After 2 days of presentations and discussion, a Coordinating Group was elected
with AL, Brazil as Chairman, Carmen Guzmán, Mexico and Marcia Otani, São
Paulo) to support the development of the reference panel.
-After some preliminary experiments, the proposals of the group were presented
by the chairman at the meeting of the Expert Committe, 8-12 october, 2007.
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
WHAT WE NEED?
Some misunderstanig on the circuntances a reference serum is employed, aroused.
STEPS ON THE NEED FOR A RELIABLE PREPARATION. WHAT FOR?
- Any organization working in diagnosis of an infectious disease need to have a suitable,
reliable, serum, from a surely infected patient, the same used in different countries.
-A) idea (thinkers): university/foundation: creates a diagnostic test in a support, with selected
antigens and get good results > publication (“in house” phase).
-B) building (makers): an industry start to invest and gets a reliable test, with reproducible
results.
-C) application (users): blood banks/diagnostic labs buy the product (kit) and get reliable and
repetitive results
-B and C need reliable sera for quality control
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
WHAT WE NEED?
KINDS OF REFERENCE SERA AND PANEL OF SERA
CHARACT.
INTERNATIONAL
PANEL OF
PANEL FOR
REFERENCE
SERA FOR
EXTERNAL
SERUM
TEST KITS
QUALITY CONTROL
----------------------------------------------------------------------------------------------------------------Nr. samples
01
200
6/panel
Volume/aliquot
0.5/1.0 mL
0.5/1.0 mL
0.5/1.0 mL
Renewal each
5 years
1 year
each 4 months
Nr. samples/5 y.
1
1.000
6x3x5y=90
Total volume
2/3 L/sample
2-5 mL
If 100 labs=100 mL/each
Origin of serum
blood donors
may be patients
blood donors
Mixtures
needed, few
not recommend.
Not recommended
Strenght
medium
mixed(high+low) medium
Etical issues
informed consent
informed consent informed consent
-----------------------------------------------------------------------------------------------------------------
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
ACCORDING TO RECCOMENDATIONS OF THE CONSULTATION
GROUP
- Need for two Reactive sera. TcI & TcII.
- Need for a negative control. Check if exists for
other diseases. Perhaps a naive requirement
- Consensus in the antibody concentration, for both
reactive. Should be relatively low, not high.
- In a scale (IFI) from 1/80 to 1/10.240, 160-640
- In ELISA, O.D. 2 – 2 ½ higher than cut-off
- Need 2 different sources, i.e. Mexico & Brazil
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
ACCORDING TO RECCOMENDATIONS OF THE CONSULTATION
GROUP
- Need 1.5 – 3.0 L (3.000 vials with 0,5 – 1,0 mL/each.
- Operational and etical problems, if from single, infected.
- More feasible from a pool of few positives.
- Alternatively, (or/and) start from high responder
donor, dilute with negative, look for end point.
- Explore both, pool of high titer, then diluted
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
ACCORDING TO RECCOMENDATIONS OF THE CONSULTATION
GROUP
- First issue: is possible to dilute a high ab concentration
sera, and, until what dilution, without loose titer?
- A well doccumented serum from an infected and another
from non-infected were experimented, as follows:
- 1:1 (final dilution 1/2, i.e. 100 uL posit.+ 100uL negative)
- 1:2; 1:3, 1:4, 1:5, 1:10, 1:20, 1:50, 1:100
- results showed clearly positive up to 1:5 - 1:10.
- higher dilutions were not possible to use.
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
PRELIMINARY EXPERIMENTS FOR EXPLORE FEASIBILITY OF
SERUM DILUTION
DIL
ELISA EL.Bio EL.Wie IIF
Conclusion
--------------ratio
ratio
ratio
titer
------------------------ Positive
pure
4.1
5.5
6.6
1/5120 approve (as positive)
- P(1)+N(1)
1:2
3.8
5.2
7.4
1/2560 ok
- P(1)+N(2)
1:3
3.2
4.6
7.2
1/1280 ok
- P(1)+N(3)
1:4
2.8
4.4
6.2
1/640 ok
- P(1)+N(4)
1:5
3.0
3.9
5.7
1/640 ok
- P(1)+N(9)
1:10
2.3
3.2
4.0
1/320 to discuss
- P(1)+N(49)
1:50
1.1
1.3
0.7
1/80
bord/not useful
- P(1)+N(99)
1:100
0.8
1.1
0.1
1/10
negative/not to use
- Negative
pure
0,5
0.4
0.1
<1/10 approved (as negative)
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
PRELIMINARY EXPERIMENTS FOR EXPLORE FEASIBILITY OF
SERUM DILUTION (Exp. Done in Mexico, by Dr.Gusman)
DIL
ELISA ELISA 2
Conclusion
- Positive
pure
4.9
5.4
approved (as positive)
- P(1)+N(1)
1:2
3.9
5.3
ok
- P(1)+N(2)
1:3
3.3
4.7
ok
- P(1)+N(3)
1:4
2.8
3.8
ok
- P(1)+N(4)
1:5
2.3
3.4
ok
- P(1)+N(9)
1:10
1.6
2.6
to discuss
- P(1)+N(49)
1:50
0.5
0.9
Bord/not useful
- P(1)+N(99)
1:100
0.3
0.6
negative/not to use
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
BRAZILIAN SELECTION OF SAMPLES FOR PREPARATION OF WHO REF. SERA
- All samples from Hemocentro, São Paulo, HC, USP.
- Selection performed by one member of the coordinating group, Dr. M.Otani
- 4 plasmas selected primarily
-Identification,
date collection,
date born, place/locality
-A) 103.350.016,
-B) 103.362.946,
190307,
190207,
160850,
030477,
La Canela (Chile),
male,
residence SP.
Januaria, MG,
female
endemic
until
28y, female, maternal uncle Chagas
-C) 103.372.121,
-D) 103.402.366,
110407
030507,
260757,
Buique, PE,
- A) 016
- B) 946
- C) 121
- D) 366
ELISA2,duplic
1,52-1.39/0,25
1.62-1.56/0.26
1.17-1.11/0,26
1.50-1.41/0,26
ELISA 3
2.40/0,26
2.38/0.26
1,54/0.26
1.24/0.26
IIF(SP)
1/640
1/160
1/160
1/160
first ELIS
2,05/0,26
1.93/0,26
0.96/0,26
1.68/0.26
ElWi
8.3
8.1
8.3
8.1
sex,
female
epidemiology
endemic
until
40y
IIF (GO) Conclusion
>1/5120 SUITABLE
>1/5120 SUITABLE
1/1280 wait
1/1280 SUITABLE
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
PRELIMINARY MIXTURES FOR PREPARATION OF A
REFERENCE SERUM, BRAZIL (Dr. Marcia Otani)
-Serum A
-60 mL
+ serum B
+180 mL
+ serum D
+ 60 mL
+ neg serum = mixture A.
+ 1.200 mL =1.500 mL
-São Paulo
- ElLemosAR ElBiomer
- 0.86/0.19 0.98/0.26
-RI 4,53
3.80
Goiania
ELISA 2
1.04/0.36
2.91
ElWien IIF
1/1280
7,3
-Comments: technically acceptable preparation.
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
NEXT STEPS FOR A REFERENCE PANEL OF SERA (2007)
(presented to the Expert Comittee on Biological Standardization, October, 2007)
- Mexico is planning to send the 1,5 L of a pool of 5 donors in nov.
- To discuss the need for a negative control for endemic area
- To re-check for absence of HIV, hepatitis B, other markers
- To check each one of the mixtures with IHA, different trades of IIF
- To check with ELISAS available in BR, AR, PY, CH, MX.
- To check results with rapid tests available
- To check for Reumatoid Factor and IgM anti-T.cruzi
- To send pools for liophilization.
- To distribute samples to different industries/manufacturers x analysis
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
NEXT STEPS FOR A REFERENCE PANEL OF SERA (2008)
-WHERE WE ARE? (OCTOBER 2008)
- After one year of presentation to the Expert Committee:
- Mexico made progress by sending to São Paulo the 1,5 L of serum
from several
donors.
- Samples are frozen down, waiting orders/authorization from WHO/Geneve.
- Due to administrative problems in WHO, the meeting of Chagas was posponed.
- Due to the same problems the Expert Committee was held in october, no Chagas
-NEXT STEPS:
- To check preparations with ELISAS available in BR, AR, PY, CH, MX, US.
- To check results with rapid tests available
-To send pools for liophilization.
- To distribute samples to different industries/manufacturers for analysis
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
FINALLY, WHAT DO WE NEED?
- A lyophylized batch of aprox. 1,500 aliquots of serum, with 0.5 – 1.0 mL each, with
antibodies anti-T.cruzi in such a concentration that most/all available, good quality
reagents prepared with T.cruzi 2 Ag will be able to detect. This serum will be
prepared from T.cruzi 2 patients.
- To prepare a similar batch from sera from donors of T.c 1 area
- As these preparations may be used for calibration of reagents, they should not have
high concentration of Ab, but enough to allow their detection by most already known
kits, without further manipulation.
- We will not prepare panels of sera, but a single pair of reference sera
- Even if some wanted to have also a negative control, we do not agree
- These preparations will be available to all those who need a stable and reliable
sample of serum with antibodies against T. cruzi
PROPOSAL OF A REFERENCE PANEL FOR CHAGAS
FINALLY, WHAT DO WE NEED? FOR WHOM?
- These preparations will be available to all those who need a stable
and reliable sample of serum with antibodies against T. cruzi (under
WHO regulations)
- 1) Blood banks, to calibrate their reagents and prepare a panel
-2) Diagnosis labs, for same purposes
-3) Manufacturers, to have a reference sample to test against new panels of
sera.
-(suggested use: 2 – 3 times / year, together with internal controls, when new reagents
are employed or new lots)