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26/09/2014
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Wornei Braga
Alice Springs - 2014
300 indigenous ethnic groups
76.687 Km²
12.000 inhabitants
3.000 Rural zone
5.000 indigenous
JAVARI
Study area
Terra Indígena do Vale do Javari e situada no Estado do Amazonas, ocupado por povos: Mayuruna, Marúbo, Kulína, Kanamary, Matís e Kurúbo, demarcada e homologada em 2000. Javari Valley
MATIS MARUBO
KORUBO
KANAMARI KULINA MAYURUNA
SURVEILLANCE OF ICTERIC SYNDROMS IN THE VALLEY FROM
1989–2003
Conclusion • Occurrence of Falciparum malaria;
• Serological evidences of hepatitis A , B and D;
• Lábrea black fever;
• Lack of good quality information;
• Recommendation to implement a surveillance program of viral hepatitis for the indigenous population.
Serological survey 2006
Background
HBsAg – samples anti-HBCT reactive
and anti-HBs non reactives;
Anti-HDT – all anti-HBcT reactive ;
HBsAg reactives – HBeAg, anti-Hbe,
anti-HBc IgM
≈ 2.700 samples tested
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ETNIA HBsAg ANTI-HBCT ANTI-HVD
MAYURUNA 9,1% 53% 66%
MATIS 6,0% 50% 18%
MARUBO 8,6% 51% 45,6%
KANAMARY 5,5% 53% 30%
KULINA 11,1% 60% 80%
KORUBO 0 11,1% 0
NON INDIAN 13% 52% 66%
HBV Distribution among ethnic groups, Javari Valley 2006.
≈ 400 HBsAg carriers
Treatment of those with compensated liver disease
Ultrasound Liver biopsy
HBsAg carriers
Biochemistry and hematological tests
Clinical evaluation
PEGUILATED INTERFERON ALFA 2A MONOTHERAPY 48 WEEKS
HEALTH SUPPORT HOUSE IN TABATINGA
CLINICAL ASPECTS
GENDER – WOMAN, 23 YEARS;
ETHNIC GROUP - MATIS;
HBV INFECTION DIAGNOSED DURING PRE-NATAL EXAMS
2010;
HBV/DNA +;
HDV/RNA +/ HDV-3;
TREATMENT - AUGUST 2011;
PEGUILATED INTERFERON 48 WEEKS;
STOMACH PAIN – TREATED.
Paraíso village/ Matis Alvarenga 2014
Evaluation Achado
Fibrosis Cihrosis
Portal Inflammation Moderate
Bridging necrosis Present
Ht% Hb g/dl Leuco /mm³ Plt/mm³ BT mg/dL ALT UI/l AST UI/l GGT UI/l
02/07/2011 31,8 10,9 5300 134000 0,61 55 37 19,7
HBsAg HBEAg ANTI-HDV ANTI-HCV PCR –HDV copies/mL LOG-HDV PCR-HBV-UI/mL
Reactive Non reactive Reactive Non reactive 20.482 4,31 <20
Hematologic and biochemistry profile pre-treatment
Serology and molecular tests
METAVIR score A2F4
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Moderate activity Regenerative nodule
Fibrosis Perisinuisodal fibrosis
HBsAg HBEAg ANTI-HDV ANTI-HCV
PCR –
VHD
copies/
mL
LOG-
HVD
PCR-
VHB-
UI/mL
2011
pre Reactive
Non
reactive Reactive
Non
reactive 20.482 4,31 <20
2012
pos Reactive
*
Reactive
Non
reactive <75 <1,88 <20
2014 Reactive * Reactive Non
reactive * * *
Serology and molecular tests pre and pos treatment
* Not known
Variable N Advance
d fibrosis % OR 95%CI
p
value OR* 95%CI* p value*
Total 64 32 50
Gender
M 43 23 53.5 1.53 0.53-4.38 0.42
F 21 9 42.9
Age group
> 25 28 18 64.3 2.82 1.01-7.87 0.04 4.05 1.13-14.50 0.03
≤ 25 36 14 38.8
Splenomegaly
Y 36 23 63.9 3.73 1.31-10.61 0.01 2.41 0.75-7.78 0.13
N 28 9 32.1
HBV viral load
≥ 2 log 9 6 66.7 2.23 0.50-9.83 0.28
< 2 log 55 26 47.3
Delta
predominance
≥ 2 log 36 24 66.7 5.00 1.70-14.6 0.003 6.47 1.79-23.37 0.004
< 2 log 28 8 28.6
* multiple logistic regression; N= number of subjects; OR= odds ratio; 95% CI= 95% confidence interval; Y=
yes, N= no; Gender= M= male, F= female
Advanced fibrosis and associated variables of the 64 patients with chronic
HDV/HBV coinfection included in the study and multiple logistic regression
Braga et al., 2014. Journal of Hepatology
* multiple logistic regression; N= number of subjects; OR= odds ratio; 95% CI= 95% confidence interval; Y=
yes, N= no; Gender= M= male, F= female
Advanced necroinflammatory activity and associated variables of the 64 patients with
chronic HDV/HBV coinfection included in the study and multiple logistic regression
Variable N Advanced
inflammatory activity
% OR 95%CI p
value OR* 95%CI*
p value
* Total 64 44 68.8
Gender M 43 30 69.8 1.15 0.37-3.52 0.80 F 21 14 66.7
Age group > 25 28 20 71.4 1.25 0.42-3.65 0.68 ≤ 25 36 24 66.7
Splenomegaly Y 36 30 83.3 5.00 1.58-15.75 0.006 4.09 1.18-14.1 0.02 N 28 14 66.7
HBV viral load ≥ 2 log 9 9 100 underfined 0.00->1.012 0.95 < 2 log 55 55 63.6 Delta
predominance
≥ 2 log 36 31 86.1 7.15 2.15-23.78 0.001 6.09 1.73-21.3 0.004 < 2 log 28 13 46.2
Braga et al., 2014. Journal of Hepatology
ATALAIA AM37
ATALAIA AM33JD
KC590319 Gen 3 RJ-BR
L22064 Gen 3 Peru
AF251367 Gen 3 VNZ
EF150927 Gen 3 Brazil
HF679406 Gen 3 Amazonia BR
ATALAIA AM PJCM
ATALAIA AM42
ATALAIA AM34
EF150929 Gen 3 Brazil
HF679404 Gen 3 Franca
HF679405 Gen 3 Amazonia BR
EF150933 Gen 3 Brazil
ATALAIA AM146
ATALAIA AM139
AB037948 Gen 3 VNZ
AB037949 Gen 3 VNZ
L22061 gen 3 Col
ATALAIA AM20CV
ATALAIA AM149
ATALAIA AM1SBM
TABAT AM BR/33
ATALAIA AM19PBM
ATALAIA AM4FPM
ATALAIA AM58
ATALAIA AM1ADS
ATALAIA AM114M
ATALAIA AM200
TABAT AM18IAC
ATALAIA AM1EPC
ATALAIA AM88
ATALAIA AM11
ATALAIA AM34WB
ATALAIA AM11JTM
TABAT AM18
ATALAIA AM27SM
ATALAIA AM02
ATALAIA AM68
ATALAIA AM84SD
AJ583868 VHD Gen 7
AJ583888 VHD Gen 7
AM183333 Gen 7 Cameroon
U81988 Gen IC Somalia
U81989 Gen 1C Ethiopia
AB118849 Gen 1 Japan
X85253 Italy
AY261457 Gen 2a Taiwan
X60193 Gen 2 Japao
AJ309880 Gen 2 Russia
AM183327 VHD Gen 8
AX741169 VHD Gen 8
AM183330 VHD Gen 8
AM183329 Nigeria
AJ583887 VHD Gen 6
AJ583871 VHD Gen 6
AJ583884 VHD Gen 6
AM183331 Guine
AJ583877 Gen 5 Gambia
AX741154 Gen 5 Ivory Coast
AJ583886 gen 5 Camaroes
56
80
99
68
99
97
88
51
94
80
76
76
95
55
99
95
52
58
0.05
MOLECULAR ASPECTS
Braga et al., 2014. Journal of Hepatology
Multiple alignment of the LHDAg C-terminus of the 28 sequences compared with seven HDV-3 reference sequences from Brazil, Peru, Colombia, Venezuela and France.
2014 - visit
Look over 2006 survey
Village Paraíso
Matis
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INDIGENUOS AGE (YEARS) GENDER HBsAg 2006 TREATMENT HBsAg 2014
2006
1 1 M 1 UnT A
2 5 F 1 UnT 2
3 5 F 1 UnT A
4 6 F 1 UnT 2
5 6 F 1 UnT 2
6 7 F 1 UnT 2
7 9 M 1 UnT A
8 11 F 1 UnT 2
9 16 M 1 UnT 1
10 22 F 1 UnT 2
11 26 F 1 UnT A
12 27 M 1 UnT A
13 27 F 1 UnT A
14 29 M 1 UnT 2
15 34 F 1 UnT 2
16 42 F 1 UnT 2
17 42 F 1 UnT A
18 53 M 1 UnT A
19 21 M 1 T A
20 23 M 1 T A
21 23 M 1 T 2
22 23 F 1 T 1
23 25 M 1 T A
24 55 M 1 T 2
2014
25 27 F 2 UnT 1
26 43 F A UnT 1
27 52 M A UnT 1
28 68 F A UnT 1
Year Samples Reactives Prevalence
2006 352 indigenous 24 positives 6.8%
2014 263 indigenous 6 positives 2.3%
M – male; F – female; 1 - positive; 2 – Negative; UnT – not accepted, T - accepted treatment ; A - absent
Distribution of the study population by age, gender, year of test, HBsAg status and treatment
HBsAg prevalence in the Matis per year of survey (2006 and 2014)
Pupuri
Nazare
Maraha
Amparo
Samauma
Realeza
Maceari
Limeira
Hermida
Estacao
Tamacuru
Sepatini
Sao JoseSanta Fe Meteripu
Capacini
Vila Dede
Sao Paulo
Lusitƒnia
Igualdade
Cachoeira
Novo Brasil
SÆo Geronimo
Praia GrandeVargem Grande
Santa Eugenia
Praia do Gado
Boca do Ituxi
Praia do Pirao
Boca do Passia
Praia de Labrea
HBsAg 6,6%
A-HBc T 68,9%
A-HDV 50,0%
HBsAg 6,9%
A-HBc T 63,6%
A-HDV 66,7%
HBsAg 8,6%
A-HBc T 40,0%
A-HDV 66,7%
HBsAg 6,9%
A-HBc T 73,1%
A-HDV 29,0%
HBsAg 0,0%
A-HBc T 45,0%
A-HDV 0,0%
HBsAg 12,0%
A-HBc T 56,0%
A-HDV 0,0%
HBsAg 3,2%
A-HBc T 43,0%
A-HDV 0,0%
HBsAg 0,0%
A-HBc T 36,4%
A-HDV 0,0%
HBsAg 7,8%
A-HBc T 54,9%
A-HDV 50,0%
HBsAg 0,0%
A-HBc T 45,8%
A-HDV 0,0%
HBsAg 34,0 %
A-HBc T 75,4 %
A-HDV 0,0%
HBV and HDV distribution – vilages visited
Braga, et al., 2012
Dias et al., 2012
F
D
A
Urbana area Rural area
Castilho et al., 2012
F
Male
32 years
HBV/HDV coinfection
HBV gen F
HDV gen 3
6 months evolution
Considerações
WE ARE TEACHING THE INDIGENOUS PEOPLE FROM JAVARI
VALLEY WHAT IS HEPATITIS
INDIGENOUS PEOPLE
HISTORICAL CONTEMPORANEOUS PERMANENT NATURE
AUTO DETERMINATION CITIZENSHIP AND FUTURE.
FINAL CONSIDERATIONS
Thank you !