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Wornei Braga

Alice Springs - 2014

wornei.braga@hotmail.com

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 !