Mosquitos, Viruses and Humans, two are OK, three too much

JOSÉ EDUARDO LEVI
VIROLOGY LAB
TROPICAL MEDICINE
INSTITUTE,
UNIV. OF SÃO PAULO, BRAZIL
” Mosquitos, Viruses and Humans,
two are OK, three too much”
NUMBER OF NOTIFIED CASES
BRAZIL – 2016 (UP TO AUGUST, 13th)
1,426,005 DENGUE (509 deaths)
1:2,801
216,102 CHIKUNGUNYA (91 deaths)
1:2,374
196,976 ZIKA (3 deaths)
1:65,658
1685 – First outbreak of Yellow Fever in
Recife, Brazil, introduced from the
Caribbean.
XVIII Century – No YFV outbreaks recorded
XIX Century – Huge outbreaks all over the
country
1951 – Dr Max Theiler
Wins the Nobel Prize for
the successful Y17D vaccine
1958 – After decades of
fight against Aedes aegypti
it was declared
eradicated in Brazil.
1984 –Aedes aegypti
is again present in all
Brazilian states
1986 –Aedes albopictus
is described for the first
Time in Brazil (Rio de Janeiro)
DENV1
1,400,000
DENV1/4 100,000
Probable Cases
DENV2
Hospitalizations
1,200,000
90,000
80,000
70,000
1,000,000
DENV3
800,000
DENV1
600,000
60,000
50,000
40,000
30,000
400,000
20,000
200,000
10,000
0
0
86 88 90 92 94 96 98 00 02 04 06 08 10 12 14
CHIKV 2014/2015
CHIKV 2016
ZIKA INTRODUCTION TO BRAZIL
THERE ARE FOUR HYPOTHESES
1) TRAVELLERS FROM EASTER ISLANDS (2014)
2) 2014 WORLD CUP SOCCER TOURNAMENT (JUN 12TH - JUL 13TH)
3) THE VA’A CANOE EVENT HELD IN RIO DE JANEIRO BETWEEN 12-17
AUG 2014.
4) 2013 CONFEDERATIONS CUP SOCCER TOURNAMENT (15TH-30TH JUN
2013)
88 PREGNANT WOMEN
WITH RASH WERE INVESTIGATED
72 ZIKV+
16 ZIKV-
2 MISCARRIAGES
42 US PERFORMED(60%)
12 ABNORMAL (29%)
2 STILLBIRTHS
16 US PERFORMED
0 ABNORMAL (0%)
NOV. 2015
NOVEMBER 2015
1,501 CASES SUSPICIOUS OF
MICROCEPHALY
WERE THOROUGHLY INVESTIGATED
899 DISCARDED AND 311 CONFIRMED
AND 291 ?
20% of the definite or probable cases presented head
circumferences in the normal range
33% had no history of a rash during pregnancy
Rashes in the third trimester of pregnancy were
associated with brain abnormalities despite normal
sized heads.
IS IT POSSIBLE TO BE RE-INFECTED BY ZIKV?
ZIKA CASES INCIDENCE/100,000 INHABITANTS
UP TO WEEK 27 (JULY 9TH, 2016)
Had the ”Brazilian-Polynesian” ZIKV strain acquired
mutations responsible for the neurovirulent properties?
Faria NR et al. Science 2016;science.aaf5036
WHAT IS THE RELEVANCE OF ZIKV
TO BLOOD SAFETY?
DENGUE LABORATORY MARKERS AMONG BLOOD DONORS FROM
SANTOS, BRAZIL. LEVI, UNPUBLISHED
MONTH/YEAR
JAN/2010
FEB/2010
MARCH/2010
APRIL/2010
JULY/2010
JULY/2011
MEAN
N=
500
493
495
500
500
500
IgG
IgM
IgG + IgM
TMA
74,0%
64,5%
68,7%
70,2%
71,6%
74,4%
7,2%
8,5%
15,2%
24,4%
17,8%
8,6%
5,8%
6,9%
13,7%
23,8%
17,8%
7,8%
0,0%
1,4%
1,2%
0,8%
0,0%
0,0%
70,6%
13,6%
12,6%
0,6%
30% x 30% = 9% CHANCE OF BOTH DONOR AND RECIPIENT SERONEGATIVE
Grifols (formerly Novartis) – Sponsor, Santos Dengue Blood Donors Study
14
Transfusion. 2015 May;55(5):
2016 Aug 30:1-3
TESTING FOR ZIKA RNA BY ”LAB-DEVELOPED”REALTIME PCR BLOOD UNITS FOR PREGNANT WOMEN
AND INTRA-UTERUS TRANSFUSIONS
• RESEARCH PROTOCOL
• INFORMED CONSENT
• APPROXIMATELY 10 TX/MONTH
cp/ml
3.5E+04
1.1E+04
3.5E+03
1.1E+03
3.5E+02
1.1E+02
3.5E+01
1.1E+01
3.5E+00
PFU/ml
3.81E+02
1.21E+02
3.81E+01
1.21E+01
3.81E+00
1.21E+00
3.81E-01
1.21E-01
3.81E-02
Commercial
NAT
N=7
100%
100%
100%
100%
100%
100%
100%
100%
57%
1.1E+00
3.5E-01
1.21E-02
3.81E-03
0%
14%
Plasma
Supernatant
cp/ml
4.4E+04
1.4E+04
4.4E+03
1.4E+03
4.4E+02
1.4E+02
4.4E+01
1.4E+01
4.4E+00
1.4E+00
4.4E-01
PFU/ml
9.87E+00
3.12E+00
9.87E-01
3.12E-01
9.87E-02
3.12E-02
9.87E-03
3.12E-03
9.87E-04
3.12E-04
9.87E-05
Negative
cp/ml
neg
PFU/ml
neg
Commercial
NAT
N=7
100%
100%
100%
100%
100%
100%
100%
86%
71%
43%
0%
Commercial
NAT
N=7
0%
A
B
C
D
E
F
G
H
Brazil - LevI
N=13
100%
100%
100%
85%
54%
38%
23%
0%
0%
N=3
100%
100%
100%
100%
100%
100%
67%
0%
0%
N=12
100%
100%
75%
83%
50%
0%
8%
0%
0%
N=8
100%
100%
100%
100%
100%
63%
50%
13%
0%
N=4
100%
100%
100%
100%
100%
100%
50%
50%
0%
N=4
100%
100%
100%
100%
0%
0%
0%
0%
0%
N=3
100%
100%
100%
100%
0%
0%
0%
0%
0%
N=3
100%
100%
100%
100%
25%
0%
0%
0%
0%
N=2
100%
100%
100%
100%
100%
50%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
A
B
C
D
E
F
G
H
Brazil - LevI
N=13
100%
100%
100%
100%
85%
38%
15%
15%
23%
0%
0%
N=3
100%
100%
100%
100%
100%
100%
100%
33%
0%
0%
0%
N=12
100%
100%
100%
67%
67%
25%
8%
8%
0%
0%
0%
N=8
100%
100%
100%
100%
100%
63%
63%
0%
13%
0%
0%
N=4
75%
100%
100%
100%
100%
100%
50%
50%
0%
0%
0%
N=4
100%
100%
100%
100%
25%
0%
0%
0%
0%
0%
0%
N=3
100%
100%
100%
100%
100%
0%
0%
0%
0%
0%
0%
N=3
100%
100%
100%
100%
100%
50%
25%
0%
25%
0%
0%
N=2
100%
100%
100%
100%
100%
100%
0%
0%
0%
0%
0%
A
B
C
D
E
F
G
H
Brazil - LevI
N=13
0%
N=3
0%
N=12
0%
N=8
0%
N=4
0%
N=4
0%
N=3
0%
N=3
0%
N=2
0%
RESULTS
• FROM FEB/2016 – JULY/2016 – 17,000 DONATIONS
TESTED
1 ZIKA RNA+ (SANTOS-SP), in accordance to the absence of
autochtonous cases in São Paulo city
ARBOVIRUSES DETECTED IN SURVEILLANCE – SÃO PAULO
STATE
Mun. São J.R.Preto
- Vírus da Febre
Amarela
Mun. Pereira
Barreto
-Vírus Saint Louis
Mun. Guarulhos
-Vírus Ilheus
- Vírus Tensaw
Mun. Araçatuba
- Vírus Saint Louis
Mun. Salesópolis
-Vírus Boraceia
- Vírus Mucambo
-Vírus Anhembi
- Melao
- Guaratuba
- Manzanilla
- Icoaraci
- Saint Louis
- EEE
Mun. Cotia
-Vírus Cotia
-Vírus Tacaiuma
-VEEE
Mun.Itapetininga
- VEEE
- Vírus Saint Louis
- Anhembi
- Guaratuba
- Manzanilla
- Icoaraci
- Cotia
Mun. Guarujá
- Turlock
Mun. Miracatu
- VEEE
-Vírus Rocio
Município Buri
- Vírus da Febre
Amarela
Mun. Cananéia
- Cananeia
- Bruconha
- Enseada
- Cotia
- Guaratuba
- Rocio
- Bertioga
Mun.
Bertioga
- Bertioga
- Guaratuba
- Caraparu
- EEE
- Saint Louis
- Wyeomyia
- Mirim
- Manzanilla
- Icoaraci
Município de Iguape
Vírus Rocio
Vírus Manzanilla
Vírus Iguape
Vírus Itimirim
VEEE
Vírus Tacaiuma
VVEE
Vírus Guaratuba
Vírus Caraparu Vírus Cananeia
Vírus Mucambo Vírus Cotia
Vírus Maguari Vírus Mirim
Mun. Peruíbe
- Cotia
- Caraparu
São Paulo
15,000,000 inhabitants
< 5,000 dengue cases/year up to
2013
2014- 30,000
2015- 100,000
60 KM
Santos
800,000 inhabitants
>20,000 dengue cases in 2001
(DEN3)
 20,000 dengue cases in 2002
(DEN3)
> 35,000 dengue cases in 2010
(DEN2)
WILL OTHER ARBOVIRUSES EMERGE?
PROBABLY, BUT WHEN AND WHERE IT IS UNPREDICTABLE!
WHAT CAN BE DONE IN PREVENTION?
VACCINES – YES, BUT HOW MANY?
ELIMINATE THE VECTOR – HOW?
TRANSGENIC AEDES
WOLBACHIA
OTHER STRATEGIES
ACKNOWLEDGMENTS
FUNDAÇÃO PRÓ-SANGUE
DR ALFREDO MENDRONE AND TEAM
HOSP. ISRAELITA ALBERT EINSTEIN
DR JOSÉ MAURO KUTNER AND TEAM
VIROLOGY LAB., IMT-USP
DR CLÁUDIO PANNUTI AND TEAM
DR CELSO BIANCO – ISBT PRESIDENT
FAPESP GRANT 2014/50093-8