How To Collect and Evaluate Surveillance and Epidemiologic Data For Hepatitis C

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How To Collect and Evaluate Surveillance and
Epidemiologic Data For Hepatitis C

• Miriam J. Alter, Ph.D.
• Division of Viral Hepatitis
• Centers for Disease Control and Prevention
• Atlanta, GA USA

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Surveillance for Hepatitis C Virus Infection
Detect outbreaks Assess disease/infection burden
Monitor trends Identification follow-up of
infected persons Develop, implement, evaluate
prevent programs Guide allocation of resources
Acute disease
All infected persons
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Surveillance Components

• Case reporting
• Prevalence assessment and monitoring
• Special studies

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Establishing Surveillance

• Standardized case definitions
• Reliable laboratory reporting
• Infrastructure for identifying cases
• Identify biases that affect interpretation of
  data
• Generalizability of cases identified
• Testing and reporting practices
• Determine types of information to be collected

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Anti-HCV EIA RR Results by RIBA 3.0 and
Population Tested
RIBA 3.0
Source LY Hwang, Houston R. Gunn, San Diego S.
Harris, Austin I. Weisfuse, NYC CDC, Atlanta
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Proportion of Anti-HCV RR EIA Results Testing
RIBA Positive by S/CO Ratio
(N765)
(N18)
(N21)
(N231)
EIA S/CO Ratio
Source LY Hwang, Houston R. Gunn, San Diego S.
Harris, Austin I. Weisfuse, NYC CDC, Atlanta
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ALT levels in HCV-infected persons
Acute Hepatitis C ( n267)
7 x ULN
85
15
Chronic HCV infection (n4702)
3
97
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Epidemiologic Studies

• Identify persons at risk for infection
• Determine amount of disease/infection
  attributable to each risk factor
• Provide guidance for surveillance and prevention
  programs

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Types of Epidemiological Studies

• Cohort (prospective) - direct estimate of risk
• Presence of exposure determined in sample of
  population
• Entire sample followed and incidence of disease
  compared for those with and without the exposure
• Case control (retrospective) - indirect estimate
  of risk
• Sample selected based on presence or absence of
  disease
• Proportion of cases with history of exposure
  before onset of disease compared with controls
• Cross-sectional or prevalence - associations
• Presence of disease determined in sample of
  population
• Proportion of cases with history of exposure
  compared with non-cases
• Prevalence of disease compared for those with and
  without the exposure
• Temporal sequence of exposure relative to disease
  unknown

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Cohort Studies

• Directly measure relative risk and population
  attributable risk
• Require large sample sizes, long follow-up,
  expensive
• Only evaluate a single exposure

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Case Control Studies

• Sample size, logistics, and expense reasonable
• Odds ratio good estimate of risk if certain
  assumptions met
• Frequency of disease in population small
• lt2 incidence/year
• Cases and controls representative -- CRITICAL
• Will not detect rare events

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Prevalence Studies

• Logistics less complex, less expensive
• Determining specific exposures preceding
  infection problematic when onset unknown or many
  years ago
• Substantial differences in methodology
• Population-based
• Highly selected groups
• Blood donors
• Clinic patients
• Inconsistent results among studies
• Under-ascertain some risk factors
• Cannot generalize to the rest of the population

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Sources of Study Populations That Affect Reliable
Interpretation of Results
Controls
Cases

• Disease vs asymptomatic
• Single source
• Referral (e.g., GI clinic)
• Clinics serving disadvantaged population
• Highly specialized setting for specific condition
• Case reports

• Blood donors
• Family member
• Cases of other types of viral hepatitis
• Single disease group

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Risk Factors Associated With Acquiring HCV
Infection, United States
Cohort and Case Control Studies

• Transfusion, transplant
• Injecting drug use
• Occupational blood exposure (needle sticks)
• Birth to an infected mother
• Infected sex partner
• Multiple heterosexual partners

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Exposures Not Associated With Acquiring HCV Case
Control Studies of Acute Hepatitis C, U.S.,
1979-1985
Cases Controls Exposure (prior 6 months) n148
n200 Medical care procedures 30.4 29.5 Denta
l work 24.3 23.5 Health care work (no blood
contact) 4.1 5.0 Ear piercing 2.7
3.0 Tattooing 0.7 0.5 Acupuncture 0
1.0 Incarceration 4.1 1.0 Foreign travel
4.1 2.5 Military service 1.3 4.9
Source JID 1982145886-93 JAMA 19892621201-5.
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HCV Related to Health-Care ProceduresUnited
States

• Not associated with sporadic or background
• Recognized primarily in context of outbreaks
• Contaminated equipment
• Hemodialysis
• Unsafe injection practices
• Plasmapheresis
• Multiple dose medication vials
• Hospitalized patients
• Private practice
• Home infusion therapy

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Cross-sectional/Prevalence Studies of HCV
Variation of Results Low Prevalence Countries
Donors Patients College Exposure US
US AU UK GI Spinal VA Students
Injecting drug use ND Transfusion
ND - Tattooing - - - - Nasal
cocaine use - ND ND ND ND - - Ear/body
piercing /- ND - - ND - Acupuncture - - ND
- - - - ND Incarceration -
- ND ND ND
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History of Tattooing and Acute Hepatitis
C1982-2000, United States
Time period of History of tattooing prior
6 mo reported case N All patients No
IDU/BT
Total (95 CI) 1856 3.2 (2.5-3.8) 1.5
(0.9-2.1) 1982-1986 839 2.7 1.8 1987-1990 625 2.
7 1.1 1991-2000 392 4.3 1.5
Source CDC Sentinel Counties Study
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History of Body Piercing Acute Hepatitis B and
Acute Hepatitis C 1996-2000, United States
History of piercing prior 6 mo Type
N All patients No IDU
Acute hepatitis B 603 2.3 1.5 Acute hepatitis
C 134 3.7 1.0
Other than ears
Source CDC Sentinel Counties Study
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Tattoos and HCV InfectionCross-sectional, GI
Clinic, Albuquerque, 95-96

• 40 Hispanic, 40 indigent
• Cases referred for positive HCV test
• Controls gastroesophageal reflux disease
• HCV status not ascertained

• Positive (total tested) Adj. (95
• Exposure Cases Controls OR CI)
• IDU or BT 87 (477) NA
• Tattooed
• Subset (no IDU/BT) 43 (58) 16 (58) 5.9
  (1.1-30.7)
• Of total cases 5 (477) 1 (58)
• Attributable fraction 0.8 (estimated from data)

Balasekaran et al. Am J Gastro 1999941341-6
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LimitationsBalasekaran et al. Am J Gastro
1999941341-6

• Representativeness
• Cases not representative of all persons with HCV
• Controls not representative of nondiseased
  persons
• Is prevalence of characteristic under study same
  in control group as in the general population?
• Possible selection bias from using a single
  disease group
• Not tested for HCV
• History of incarceration not ascertained
• Even if tattooing associated with HCV in this
  group, accounts for lt1 of infections

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Tattoos and HCV Infection Prevalence, Orthopedic
Spinal Clinic, Dallas, TX 91-92

• Over represented blacks, hisp, men, middle/low
  income
• 43/626 HCV positive (6.9 sample 2.8
  standardized)

HCV positive Adj. (95 Exposure Yes
No OR CI) AR
Tattoo 22 3.5 NA 41 Commercial
parlor 33 3.5 6.5 (2.9-14.8) (30) Beer
drinker 12 5 4.0 (1.8-8.7) 23 Injection drug
use 37.5 5 NA 17 gt1 yr 58 5 23.0
(7.5-70.6) (14) Male Ancillary HCW 32 6 9.6
(3.8-24.3) 8 Transfusion 4 7.5 NS --
Attributable risk adjusted for other risk
factors and standardized to population
Source Haley et al. Medicine 200180134-51.
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LimitationsHaley et al. Medicine 200180134-151

• Population not representative
• Inconsistent with virtually all other studies
• Dose response relationships inconsistent for
  tattooing, but not for IDU
• IDU likely under-reported
• gt50 of HCV-positives admit to IDU when
  re-interviewed after receiving results
• Some factors likely surrogates for known risks
• Male ancillary HCW (why not females?)
• Beer drinking (why not other forms of alcohol?)

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HCV and HBV Among College Students 18-35 yrs old,
U.S., 2000-2001
Positive Characteristic Total Tested
() HCV HBV
Transfusion Yes 337 (4.5) 6.2 11.8 No 7236
(95.5) 0.7 5.6 IDU Yes 116 (1.5) 22.4 17.1 N
o 7718 (98.5) 0.6 5.7 Tattoo Yes 1430 (20.5)
0.3 5.3 No 5533 (79.5) 0.5 6.2 Body
piercing Yes 1202 (17.4) 0.4 3.7 No 5701
(82.6) 0.4 6.5 Snorted drugs Yes 617 (9.1)
0.6 6.8 No 6179 (90.9) 0.4 5.9
plt.001 excluding IDU and transfusion
Hwang et al., unpublished data
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Geographic Differences in HCV Transmission
Patterns
Importance of Exposures by HCV
Endemicity
Exposures among prevalent infections Low
Moderate High

Injecting drug use Transfusions
(unscreened) Health-care related
Contaminated equipment /- Unsafe
injections /- Folk medicine -
No data






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HCV Related to Therapeutic and Cosmetic
Procedures in Moderate/High Endemic Countries

• Associated with background infections in some
  studies
• unsafe therapeutic injections
• hospitalization, surgery, dental work
• Control populations may not have been
  representative
• Acupuncture (one village in Japan)
• Geographic clustering by age, town, region
• considerable variation within and between
  countries

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Health-Care Procedures and HCV InfectionModerate
Endemic Countries
Surgery
Dental Country HCV Pos HCV Neg HCV Pos HCV
Neg Case-Control Italy 17
2 22 11 Cross-Sectional Italy 56 36 9
1 80 77 57 90 90 Taiwan 13
3 24 28 Pakistan No
data 33 39 Japan 32 10 No data
Plt.05, independent of other risk factors
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Cosmetic Procedures and HCV InfectionModerate
Endemic Countries
Tattooing Body
Piercing Country (author) HCV Pos HCV Neg HCV
Pos HCV Neg Case control Taiwan (Chen)
0 0 0 1 Cross sectional Taiwan
(Sun) 3 1 -- -- (Ho) 21 34 78
83 Japan (Kiyosawa) 1 0 -- -- 3
0 -- -- Pakistan (Luby) 7 0 7 0
Korea (Kim) 11 7 14 20
Ear piercing women only