Example of Slide

Risk Factors for Hepatitis C Virus infection

among Blood Donors in Northern Thailand:
Matched Case-Control Study
Lakkana Thaikruea 1,
Satawat Thongsawat 1,
Niwat Maneekarn 1,
David L. Thomas 2,
Dale Netski 2,
Kenrad E. Nelson 2,
1 Departments of Community Medicine, Medicine, and
Microbiology, Chiang Mai University, Chiang Mai, Thailand

2 Departments of Epidemiology & Medicine, Johns

Hopkins University, Baltimore, USA
 Rationale
No effective program in Thailand to prevent HCV
infection
Lack of information of majors route of
transmission
Distribution of HCV genotypes are not well
understood
Researchers from JHU and Chiang Mai
University have conducted study about
epidemiology of HCV in northern Thailand
Blood donor is one of the study population
besides drug users, patients, and commercial
sex workers
This present study focuses on blood donor
 Specific aims
Blood donors in northern Thailand
1. To investigate the potential risk factors
for HCV infection
2. To determine HCV genotype distribution
3. To investigate relationship between HCV

genotype distribution and the routes of

transmission
Features of hepatitis C virus infection
100
-
-
15% 85%
R e s o lv e 15 C h r o n ic 85
-
-

80% 20%
S ta b le 68 C ir r h o s is 17
-
-

75% 25%
S ta b le 13 M o r ta lity 4
-
-
-
Background: Route of transmission
USA:
IDU1, sex with an IDU,
blood transfusion among non-IDU
REDS2:**
male, black, 30 to 49 years,
< high school diploma,
first /only time blood donor,
blood transfusion history
1 Injection drug users ; 2 Retrovirus Epidemiology Donor Study
 HCV Genotypes

Epidemiologic marker
Six major genotypes:
- type 1 to 6, many subtypes
- nucleotide differences between genotypes are
30% of the viral sequence
- mutations occur during viral replication
Specific genotype:
- specific route of transmission
 Specific aim 1
To investigate the potential risk factors for
HCV infection among blood donors in
northern Thailand
 Methods: Specific aim 1

Setting
Design
Data collection
Data analysis
Methods (cont.)

Study setting
Faculty of Medicine, CMU
The Blood Bank
- The Maharaj Nakorn Chiang Mai hospital
- 1,800-bed capacity and the main referral center
Blood donors
- January 2001 - June 2002

- ≥ 18 years old at the time of donation/ recruitment

- Reside in the north

- Donation sites: walk-in and mobile unit

Methods (cont.)

Study design: Specific aim 1

Single masked matched case- control

Matched variables:
age, gender, donation date, donation sites

Mask:
interviewers and physicians did not know HCV
status of the participants
 Data collection
Eligible Case: blood bank EIA-3 positive
Invitation letters: 2nd letter in 2 weeks apart
Non-participants: sent their participation forms
indicating their unwillingness
Enrolment: explain, consent form
Trained health personnel of the same gender: face-to-
face interview
Physical examination
Counseling
Laboratory tests: 30 ml blood
– HCV antibodies; EIA-3, RIBA-3
– HCV RNA: RT-PCR
– HCV genotypes: direct sequencing
– Serum ALT
Data collection (cont)

Eligible cases were defined as

“confirmed cases ”
If they were HCV EIA-3 positive in blood
bank screening and had any of the following:

PCR positive, or
PCR negative with RIBA-3 positive, or
PCR negative with both
– positive high cut-off repeat EIA-3 (Abbot)
– positive high cut-off repeat EIA-3 (Ortho)
Data collection (cont.)

Eligible Control: blood bank EIA-3 negative

Randomly selection:
– 1 – 4 eligible controls per case
Matched variables:
– ± 15 days of case’s donation date
– Age ± 5 years old
– Same gender
– Same donation sites
Enrolment: same
Control:
– Negative to both screening EIA-3 and repeat EIA-3
Data collection (cont.)

SPOUSES

Spouses of cases and matched controls

– Regular sexual relations with the donor
for ≥ 3 months
– ≥ 18 years old at the time of recruitment
Enrolment: same
HCV infection:
– EIA-3 positive and
– Either PCR or RIBA-3 positive
 Flow of matched case-control study
38,340 donors
102 low cut-off EIA-3 positive
28 not eligible EIA-3 positive
372 EIA-3 pos Eligible cases

372 eligible cases

1234 eligible matched controls 618 non-responders
85 returned letters
903 responders
238 non-participants
665 participants

411 matched controls 254 eligible cases 67 false positive cases

82 matched
controls 12 RIBA-3 indeterminate
329 matched controls 175 confirmed cases
9 cases without control
166 confirmed cases
 Participation

Compared between participants and non-

participants
Cases: 254 participants (91.4%) versus
24 non-participants
– No statistically significant different
Controls:411 participants (65.8%) versus

214 non-participants
– Participants: age in years 33.2 ( VS 31.0)*
– Participants: ever donated 81.6 % (VS 61.3 %)*

* P value < 0.05

 Data analysis: Specific aim 1
Univariate analysis
– Matched odds ratio (OR) with 95% confidence interval (95% CI)
Multivariate analysis
– Conditional logistic regression
– Step-wise selection:
• alpha levels of 0.05 for entry and 0.0501 for remove
• to guide the selection of variables
– Either independent variables that were likely confounders or had
biological importance were forced in to the preliminary model
regardless of their statistical significance
Phylogenic analysis 1
– Tree was constructed from nucleic acid sequence alignments using
Neighbor joining method
– Sequence alignments were randomly permuted 1,000 times
• CONSENSE provided bootstrap values
– Reference sequences: GenBank
• programs: Gofasta1.1, BioEdit 5.9, Tree View 1.6 , PHYLIP 3.572c package ( SEQBOOT,
DNADIST, NEIGHBOR, CONSENSE)
 Results: Specific Aim 1

Demographic distribution
Multivariate
Spouses
 Demographic distribution

38,340 donors
Marital status:
– 62.7 % single, 36.0 % married, and 1.3 % widowed
Age:
– mean 29.43 years
Gender:
– 74.5 % male
Prevalence:
– 3.8% HBsAg, 1.3% anti-HCV, 0.2% anti-HIV,
and <0.01% VDRL
Results (cont.)

166 matched sets: 166 cases and 329 controls

IDU:
– OR = 107.6, 95% CI = 14.8, 780.6
Among 60 participants with a history of IDU:
– 59 matched sets
– 58 had HCV infection
– 1 matched set: control (not case) reported IDU history
To assess whether there was any potential risk factor
other than IDU
– non-IDU were analyzed separately
 The risk factors statistically associated with HCV
infection in multivariate analysis among non–IDU.*

Variable Non-IDU Model

OR(95% CI) †

Blood transfusion 22.77 (6.03, 85.96)

Immediate blood relatives had hepatitis/jaundice 4.37 (1.34, 14.26)
At least 6 life-time sexual partners 2.66 (1.23, 5.77)
Frequency of blood donation 0.89 (0.83, 0.95)

* matched variables: gender, age within 5 years, donation site (walk-in, mobile unit), and
within 15 days of case’s donation date
 Spouses and HCV infection
108 of 166 cases had spouses: 45 spouses participated  6 infected
 Further analysis
203 of 329 matched controls had spouses: 44 spouses participated  0
 Reported risk behaviors among the pairs of HCV
infected spouse and case partner.
Pair Number Surgery Transfu Suture Injection Pierce No. of STD‡ RT- Genotype
Spouse/case† -sion therapy partners PCR§

1 female/male +/- +/- +/- +/+ +/- 2/1 +/- +/+ 7c/7c
2 female/male +/+ -/- +/+ +/+ +/+ 1/50 -/+ +/+ 3a/3a
3 female/male +/- +/- +/- +/+ +/- 1/10 +/+ +/+ 6x/6x¶
4 male/female +/- -/+ +/- +/+ +/+ 12/2 -/- +/+ 6y/3b#
5 female/male -/- -/- -/+ +/+ +/- 250/3 +/- +/+ 3a/3a
6 female/male +/+ -/+ +/+ +/+ +/- 4/100 +/+ -/+ -/7c

† reported by spouse and case partners as; + present, - absence

‡ sexually transmitted diseases
§ Reverse Transcription-Polymerase Chain Reaction
¶ 6x = B4/92 GenBank accession number D63944
# 6y = D97/93 GenBank accession number D63947
 2a D00944 J6
2c D50409 BEBE1
2b D10988 J8
4a Y11604 ED43
C04 C-0568-01 06
D11 C-0820-01 07
B05 c-0095-01 03
A04 C-0565-01 02
H04 c-0083-01 16
F09 C-0750-01 11
H10 C-0804-01 16
F03 c-0042-01 11
1000 C06 c-0122X-01 06
A12 C-0872-01 02
B10 C-0769-01 04
C04 c-0059-01 06
A06 C-0235-01 02
F11 C-0831-01 11
D03 c-0027-01 07
801 B12 C-0878-01 04
1b D90208 J
F02 C-0453-01 12
E03 C-0503-01 09
D03 C-0160-01 07

1
C06 C-0256-01 06
E12 C-0935-01 10
1c D14853 G9
845 E04 c-0062-01 10
E03 c-0040-01 09
921 E04 C-0542-01 10
B06 c-0119X-01 04
D12 C-0916-01 08
1000 B10 C-0589-01 04
F06 C-0274-01 12
D10 C-0612-01 08
A05 C-0202-01 01
F04 C-0583-01 12
G10 C-0653-01 14
H03 C-0181-01 15
E05 C-0219-01 09
950 H04 C-0564-01 16
1a AF271632 HCV1
E12 C-0740-01 10
E05 c-0104X-01 09
E06 c-0131X-01 10
E08 C-0373-01 10
E11 C-0824-01 09
C05 c-0097-01 05
D11 c-0419-01 07
A04 C-0523-01 02
E02 C-0451-01 10
F11 c-0440-01 11
8a D84264 VN405
C05 C-0210-01 05
F08 C-0374-01 12
H11 C-0851-01 15
G06 c-0136X-01 14
C10 C-0770-01 06
1000 B12 c-0349-01 04
G07 C-0345-01 13
H03 C-0512-01 15
D86/93 D63945
H06 c-0150X-01 16
H11 C-0727-01 15
E10 C-0618-01 10
F05 C-0221-01 11
H06 C-0289-01 16
B11 C-0680-01 03
A05 c-0087-01 01
G10 C-0801-01 14
H04 C-0201-01 16
B04 C-0524-01 04
A04 c-0054-01 02
B04 c-0055-01 04
D05 c-0099X-01 07

762
A04 C-0184-01 02
A08 C-0355-01 02
H02 C-0469-01 16
D97/93 D63947
1000 F04 C-0192-01 12
B04 C-0185-01 04
B4/92 D63944
C07 C-0299-01 05
G05 C-0229-01 13
E11 C-0701-01 09
B05 C-0208-01 03
H12 C-0747-01 16
9a D84265 VN004
H07 C-0354-01 15
G11 C-0703-01 13
778

6
D04 C-0581-01 08
9c D37848 Th553
H10 C-0667-01 16
A06 c-0116X-01 02
9b D37849 Th555
C03 C-0159-01 05
A10 C-0587-01 02
9b D37850 Th602
926 A12 c-0278-01 02
6a Y12083 HK2
1000 E09 C-0748-01 09
D10 C-0782-01 08
6b D37841 Th580
11a D63822 JK046
7a D84263 VN235
7d D37843 Th846
852 F10 C-0799-01 12
7c D37846 Th976
1000 G11 c-0442-01 13
B11 C-0813-01 03
G12 C-0713-01 14
C12 C-0735-01 06
7c D38078 Th571
G04 C-0198-01 14
7c D37844 Th271
A10 C-0765-01 02
G11 C-0838-01 13
7c D37845 Th552
G03 c-0044-01 13
H03 c-0046-01 15
841
C03 C-0479-01 05
E04 C-0191-01 10
A03 C-0155-01 01
A11 c-0407-01 01
F12 C-0746-01 12
E10 C-0787-01 10
A11 C-0805-01 01 5a Y13184 H1480
10a D63821 JK049
3b D49374 Tr
3b D37839 Th527
971 A12 C-0730-01 02
D04 C-0188-01 08
1000 D03 C-0502-01 07
3b D37840 Th576
952 D04 C-0532-01 08
C12 C-0915-01 06
G04 C-0559-01 14
G06 C-0276-01 14
1000 C09 C-0403-01 05
G05 c-0106X-01 13
F04 C-0545-01 12
E04 C-0582-01 10
D05 C-0216-01 07
D06 c-0125X-01 08
D11 C-0694-01 07
B06 C-0240-01 04
F05 c-0105X-01 11

3
D06 C-0259-01 08
C11 C-0817-01 05
C04 C-0531-01 06
F07 C-0344-01 11
B12 C-0732-01 04
B04 C-0567-01 04
H09 C-0763-01 15
A03 C-0470-01 01
B09 C-0291-01 03
G04 c-0066-01 14
B03 C-0474-01 03
F03 C-0504-01 11
H05 c-0109X-01 15
D04 c-0061-01 08
D07 C-0322-01 07
D08 C-0369-01 08
C03 c-0020-01 05
B03 c-0014-01 03
G03 C-0176-01 13
746
F03 C-0173-01 11
B08 C-0357-01 04
C08 C-0364-01 06
C10 C-0606-01 06
3a D17763 NZL1
B03 C-0156-01 03
A11 C-0677-01 01
E07 C-0338-01 09
E11 c-0434-01 09

989
C04 C-0187-01 06
B11 c-0410-01 03
0.1 G02 C-0466-01 14
F04 c-0064-01 12
G09 C-0754-01 13
F06 c-0135X-01 12
F10 C-0626-01 12
C11 C-0691-01 05
G03 C-0506-01 13
F11 C-0702-01 11
H05 C-0230-01 15
A03 c-0006-01 01
B07 C-0296-01 03
E03 C-0165-01 09
E06 C-0261-01 10
C11 c-0411-01 05

Phylogenic trees : 4 pairs of spouses and their case partners with the same subtypes are
displayed with bootstrap values.
 Percentage of reported risk behaviors among spouse of
cases, by HCV infection status.

Risk factors Infected Non-infected Fisher’s exact

n (%) n (%) p value
All 6 39

Age in year (mean) 35.67 37.54 0.666 *

Surgery 5 (83.3) 13 (33.3) 0.031**
Blood transfusion 2 (33.3) 5 (12.8) 0.230
Suturing 5 (83.33) 18 (46.2) 0.187
Sexually transmitted disease 4 (66.7) 9 (23.1) 0.049**

* Student’s t test
** statistically significant at alpha level 0.05
 Discussions: Specific aim 1
Potential risk factors for HCV infection
All study population:
– IDU
Among non-IDU:
– Blood transfusion
• blood bank launched HCV screening in 1992
• not all blood bank centers in Thailand started to test donors right away
• earlier generation assays did not have high sensitivity and specificity
• test was expensive and available only in secondary or tertiary health care centers
– Immediate blood relatives had hepatitis
• could be due to another hepatitis virus
• participants did not aware of the specific cause of hepatitis/jaundice
– At least 6 life-time sexual partners
Spouses
– HCV infection: 13.3% spouses of cases but none of those of controls
– parenteral exposures: more prevalent among HCV infected spouses
– sexual transmission: concordance of HCV subtypes
– acquired infection from same sources could not ruled out
 Specific aim 2
To determine HCV genotype
distribution among
blood donors in
northern Thailand
 Methods: specific aim 2

Study design: cross-sectional

Setting: same
Data collection: same
Data analysis:
– Univariate analysis
– Phylogenic analysis
 Flow of case recruitment
502 EIA-3 donors 102 low cut-off EIA-3 positive
 28 not eligible EIA-3 positive
372 EIA-3 positive Eligible cases
 13 returned letters
359 eligible cases
 81 non-responders
278 responders
 24 non-participants
254 participants
67 false positive cases
 12 RIBA-3 indeterminate
175 confirmed cases
 18 PCR negative
157 PCR positive

156 cases with genotypes
 Results of specific aim 2
Genotype distribution: about equally distributed
Type 1 = 45 (28.8%)
– 1a (53.3%)
– 1b (46.7%)
Type 3 = 57 (36.5%)
– 3a (87.7%)
– 3b (12.3%)
Type 6 = 54 (34.6%)*
– D97/93 (42.6%)
– 7c (27.8%)
– B4/92 (11.1%)
– 9c (9.3%)
– 9b (5.6%)
– 6b (3.6%)

* Higher proportion than previous studies in Thailand

 2a D00944 J6
2c D50409 BEBE1
2b D10988 J8
4a Y11604 ED43
C04 C-0568-01 06
D11 C-0820-01 07
B05 c-0095-01 03
A04 C-0565-01 02
H04 c-0083-01 16
F09 C-0750-01 11
H10 C-0804-01 16
F03 c-0042-01 11
1000 C06 c-0122X-01 06
A12 C-0872-01 02
B10 C-0769-01 04
C04 c-0059-01 06
A06 C-0235-01 02
F11 C-0831-01 11
D03 c-0027-01 07
801 B12 C-0878-01 04
1b D90208 J
F02 C-0453-01 12
E03 C-0503-01 09
D03 C-0160-01 07

1
C06 C-0256-01 06
E12 C-0935-01 10
1c D14853 G9
845 E04 c-0062-01 10
E03 c-0040-01 09
921 E04 C-0542-01 10
B06 c-0119X-01 04
D12 C-0916-01 08
1000 B10 C-0589-01 04
F06 C-0274-01 12
D10 C-0612-01 08
A05 C-0202-01 01
F04 C-0583-01 12
G10 C-0653-01 14
H03 C-0181-01 15
E05 C-0219-01 09
950 H04 C-0564-01 16
1a AF271632 HCV1
E12 C-0740-01 10
E05 c-0104X-01 09
E06 c-0131X-01 10
E08 C-0373-01 10
E11 C-0824-01 09
C05 c-0097-01 05
D11 c-0419-01 07
A04 C-0523-01 02
E02 C-0451-01 10
F11 c-0440-01 11
8a D84264 VN405
C05 C-0210-01 05
F08 C-0374-01 12
H11 C-0851-01 15
G06 c-0136X-01 14
C10 C-0770-01 06
1000 B12 c-0349-01 04
G07 C-0345-01 13
H03 C-0512-01 15
D86/93 D63945
H06 c-0150X-01 16
H11 C-0727-01 15
E10 C-0618-01 10
F05 C-0221-01 11
H06 C-0289-01 16
B11 C-0680-01 03
A05 c-0087-01 01
G10 C-0801-01 14
H04 C-0201-01 16
B04 C-0524-01 04
A04 c-0054-01 02
B04 c-0055-01 04
D05 c-0099X-01 07
A04 C-0184-01 02
A08 C-0355-01 02
H02 C-0469-01 16
D97/93 D63947
1000 F04 C-0192-01 12
B04 C-0185-01 04
B4/92 D63944
C07 C-0299-01 05
G05 C-0229-01 13
E11 C-0701-01 09
B05 C-0208-01 03
H12 C-0747-01 16
9a D84265 VN004
H07 C-0354-01 15
G11 C-0703-01 13
778

6
D04 C-0581-01 08
9c D37848 Th553
H10 C-0667-01 16
A06 c-0116X-01 02
9b D37849 Th555
C03 C-0159-01 05
A10 C-0587-01 02
9b D37850 Th602
926 A12 c-0278-01 02
6a Y12083 HK2
E09 C-0748-01 09
D10 C-0782-01 08
1000 6b D37841 Th580
11a D63822 JK046
7a D84263 VN235
7d D37843 Th846
852 F10 C-0799-01 12
7c D37846 Th976
1000 G11 c-0442-01 13
B11 C-0813-01 03
G12 C-0713-01 14
C12 C-0735-01 06
7c D38078 Th571
G04 C-0198-01 14
7c D37844 Th271
A10 C-0765-01 02
G11 C-0838-01 13
7c D37845 Th552
G03 c-0044-01 13
H03 c-0046-01 15
C03 C-0479-01 05
E04 C-0191-01 10
A03 C-0155-01 01
A11 c-0407-01 01
F12 C-0746-01 12
E10 C-0787-01 10
A11 C-0805-01 01 5a Y13184 H1480
10a D63821 JK049
3b D49374 Tr
3b D37839 Th527
971 A12 C-0730-01 02
D04 C-0188-01 08
1000 D03 C-0502-01 07
3b D37840 Th576
952 D04 C-0532-01 08
C12 C-0915-01 06
G04 C-0559-01 14
G06 C-0276-01 14
1000 C09 C-0403-01 05
G05 c-0106X-01 13
F04 C-0545-01 12
E04 C-0582-01 10
D05 C-0216-01 07
D06 c-0125X-01 08
D11 C-0694-01 07
B06 C-0240-01 04
F05 c-0105X-01 11

3
D06 C-0259-01 08
C11 C-0817-01 05
C04 C-0531-01 06
F07 C-0344-01 11
B12 C-0732-01 04
B04 C-0567-01 04
H09 C-0763-01 15
A03 C-0470-01 01
B09 C-0291-01 03
G04 c-0066-01 14
B03 C-0474-01 03
F03 C-0504-01 11
H05 c-0109X-01 15
D04 c-0061-01 08
D07 C-0322-01 07
C03 c-0020-01 05
D08 C-0369-01 08
B03 c-0014-01 03
G03 C-0176-01 13
F03 C-0173-01 11
B08 C-0357-01 04
C08 C-0364-01 06
C10 C-0606-01 06
3a D17763 NZL1
B03 C-0156-01 03
A11 C-0677-01 01
E07 C-0338-01 09
E11 c-0434-01 09
C04 C-0187-01 06
B11 c-0410-01 03
0.1 G02 C-0466-01 14
F04 c-0064-01 12
G09 C-0754-01 13
F06 c-0135X-01 12
F10 C-0626-01 12
C11 C-0691-01 05
G03 C-0506-01 13
F11 C-0702-01 11
H05 C-0230-01 15
A03 c-0006-01 01
B07 C-0296-01 03
E03 C-0165-01 09
E06 C-0261-01 10
C11 c-0411-01 05

Phylogenic trees of HCV infected blood donors. When the proportion of 1000 permuted
trees was more than 70 %, the number supporting a clade is shown.
Specific aim 3

To investigate relationship
between HCV genotype
distribution and the routes
of transmission among blood
donors in northern Thailand
 Data analysis: Specific aim 3

Univariate analysis
– Genotypes and routes of transmission
– Genotypes: type 1, 3, and 6
– Routes of transmission: Hierarchy
1) IDU
2) transfusion
3) surgery
4) other parenteral exposures
The genotypes distribution among the 156 HCV RNA- positive participants
by demographic, laboratory, and epidemiologic characteristics.
Variable Type 1 Type 3 Type 6
n (row %) n (row %) n (row %)
Median ALT (IU/litter) * 39.0 60.0 38.0
Age group
18 – 24 13 (33.3) 13 (33.3) 13 (33.3)
25 – 39 19 (29.2) 25 (38.5) 21 (32.3)
≥ 40 13 (25.0) 19 (36.5) 20 (38.5)
Route of transmission
intravenous drug usage 17 (31.5) 19 (35.2) 18 (33.3)
transfusion 10 (32.3) 11 (35.5) 10 (32.3)
surgery 10 (30.3) 10 (30.3) 13 (39.4)
other parenteral exposures 8 (21.1) 17 (44.7) 13 (34.2)
Anti-HIV positive 2 (33.3) 3 (50.0) 1 (16.7)

* Serum alanine aminotransferase; Kruskal-Wallis p value < 0.0001

 HCV genotypes distribution by routes of transmission
and possible time of exposure.
Variable Type 1 Type 3 Type 6
n (row %) n (row %) n (row %)
Intravenous drug usage (n=54)
number of years of last injection*
<5 5 (20.8) 11 (45.8) 8 (33.3)
5 -9 11 (55.0) 5 (25.0) 4 (20.0)
>9 1 ( 5.9) 3 (15.8) 6 (33.3)
Blood transfusion (n = 28)
after 1992 1 (16.7) 3 (50.0) 2 (33.3)
before 1992 9 (40.9) 5 (22.7) 8 (36.4)
* p-value 0.045
 Discussions: Specific aim 2 and 3
Serum ALT levels:
– Type 3; hepatic steatosis
Route of transmission
– No statistically significant
IDU
– Number of years of last injection
– Type 3 had the highest prevalence: < 5 years, while type 6 (> 9
y) and type 1 (5 - 9 y)
Blood transfusion
– After 1992: type 3
– Before 1992: type 1 and type 6
Discussions: Specific aim 2 and 3 (Cont.)

Phylogenic analysis
– Type 6 was more diverse
HIV
– 50% co-infected with type 3
– IDU is one of the major mode of transmission
Type 3 was introduced into northern Thailand via
IDU not long ago and type 6 was an older
epidemic than type 3
Cannot guarantee that type 6 exists before type 3
in this geographical area
 Limitations and strengths

Specific aim 1: Single masked case-control study

Limitations:
- causal relationship; temporal ambiguity
- spouses; might not represent
Limitations and strengths (cCont.)

Strengths:
- appropriate study design;
• sample size
• matched case-control
• confounding
- minimized selection bias;
• asymptomatic nature
• lacked HCV knowledge
• available of HCV test only in some secondary or tertiary cares
• self-deferral system
- minimized information bias;
• masked
• face-to-face interview
• physical examination
- minimized misclassification of HCV status;
• confirmatory tests
Limitations and strengths (Cont.)

Specific aim 2 and 3

Cross-sectional study

Limitations
- causal relationship; temporal ambiguity
- excluded low cut-off EIA-3 values;
• ethical concern,
• avoided false positive but might missed few cases
- the genotypes distribution trend: lack of
exact exposure times
Limitations and strengths (Cont.)

Strengths
- minimized selection bias
• same
• > 1 year of data collection
• high participation rate
- minimized information bias
• masked interviewers and physicians
• combined face-to-face interview and physical
examination
- quality control of laboratory
- gold standard of genotyping
 Conclusions
Specific aim 1: Risk factors for HCV infection
– Single masked matched case-control study
– IDU
– Non-IDU: blood transfusion, multiple sexual partners
Specific aim 2: Genotype distribution
– Cross-sectional study
– Types: 3, 6, 1
– Type 3: high ALT level
– Type 6: Higher proportion than previously reported
Specific aim 3: Genotype distribution and routes of
transmission
– Number of years of last injecting drugs were associated
with HCV genotype distribution
 Public health significance
Provide the information needed for the development of an
appropriate prevention strategy
– Self –deferral
– Repeat donors
HCV counseling
– Blood donation
– Patients
Amass a cohort for the parent study
- Examine disease pathology
- Viral clearance
- Antiviral therapy
Baseline information
- Transfusion safety
- Surveillance
 Acknowledgement
Johns Hopkins University, USA
– Dr. Keerti Shah, Dr. Bradley Sack, Dr. David L. Thomas, Dr. Dale Netski, and Dr. Stuart Ray, Dr. Eric Seaberg,
Dr. Alvaro Muñoz, Dr. Kenrad E Nelson
– Dr. David D. Celentano, Dr. Marie Diener West, Dr. Steffani Strathdee, Dr. Farzadegan Homayoon
– Clevetta Chandler, Pat Beatha, Aimee Freeman, Judy, Frances Burman, Barbara Gray
Chiang Mai University, Thailand
– Faculty of Medicine: Dr. Niwet Nunthajit, Dr. Vinai Suriyanon, and Dr. Watana Nawachareon,
– Department of Internal Medicine: Dr. Satawat Thongsawat
– Department of Microbiology: Dr. Niwat Maneekarn
– The Blood Bank: Nuanchean Kumthon, Ms Prakai Sompan and staff
– Department of Psychiatry
– Department of Community Medicine
University of California, San Francisco,USA
– Dr. Edward L. Murphy NHLBI Retrovirus Epidemiology Study (REDS)
Univaersity of Maryland, USA
– Dr. Thomas Strickland and Dr. Alan Fix
CONRAD project, Thailand
Thai Red Cross, Chiang Mai, Thailand
Chiang Mai Provincial Health Office, MOPH, Thailand
– Dr. Wuthikai Moungmai and Dr. Surasing Witsarujratana and staff
Div of Epidemiology, Ministry of Public Health, Thailand
– Dr. Kumnuan Ungchusak and staff
Research Institute for Health Science, Chiang Mai, Thailand
– Dr. Teera Sirisanthana, Mr. Peter Lange and staff
Fogarty AIDS International Training and Research Program
– Dr. Chris Beyrer, Denise Caloran, Nikole Frank, and Eliene Painter
Funding: NIAID/NIDA
HCV project staff
Participants
Thai people