Hepatitis A, B & C Brought to you by those ever helpful DSDC and OLS Folks!!! Danae Bixler, IDEP Vicki Hogan, STD/AIDS Stephanie Moore, Immunization Dondeena McGraw, Serology Thein Shwe, IDEP

Hepatitis A Ram Nambiar, MPH Danae Bixler, MD, MPH Infectious Disease Epidemiology Program

Hepatitis A ‘inflammation of the liver’ Recovery is the norm caused by a virus Shed in the stool of an infected person Recovery is the norm There is no treatment

Symptoms Tiredness Stomach pain Fever Dark urine Loss of appetite Yellowing of skin & eyeballs (jaundice) Nausea

Hepatitis A Surveillance Case Definition Clinical case definition An acute illness with discrete onset of symptoms and jaundice or elevated serum aminotransferase levels Laboratory criteria for diagnosis: Immunoglobulin M (IgM) antibody to hepatitis A virus (anti-HAV) positive

Case Ascertainment First step in investigation of a reported case of hepatitis A: Does the case have a (+) Anti-HAV-IgM? Does the case have acute illness with discrete onset of symptoms? Does the case have jaundice or elevated serum aminotransferase levels Must answer ‘yes’ to all 3 questions

Example - Jo Began having nausea, vomiting, diarrhea on Saturday. Developed jaundice on Sunday. Went to the doctor on Monday and her testing showed: ALT = 1035 (ULN = 40) Anti-HAV-total (+) Anti-HAV-IgM (+)

Disease Control The first priority (!)

Hepatitis A Epidemiology Incubation period 15-50 days (avg.-28 days) Infectious period begins 14 days before onset of symptoms and for 7 days after onset of symptoms

More Hepatitis A Epidemiology Reservoir Human Transmission Fecal- Oral Foodborne / Waterborne Temporal Pattern None

Infectious Period (green) onset: jaundice > symptoms Sun Mon Tues Wed Thur Fri Sat 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Onset 26 27 28 29 30 31

Transmission Fecal-Oral Foodborne / waterborne Transmitted from person to person by putting something in the mouth that has been contaminated with the stool of a person who has Hepatitis A. Includes: Not washing hands after going to bathroom or changing diapers ‘Toddler hygiene’ Some sexual practices Foodborne / waterborne Contaminated water/ice Foods that have been contaminated during handling. Virus is spread in areas with poor sanitary conditions or where good personal hygiene is not observed Blood exposure (rare)

Hepatitis A Risks People who live with or have sex with an infected person Children & staff of child care centers where a child/employee has hepatitis A Residents & staff of centers for disabled children when a child/staff has hepatitis A Travelers to countries where hepatitis A is common & where there is little clean water or proper sewage disposal

Control Measures Household and sexual contacts Educate Signs and symptoms of disease Preventing transmission Handwashing Administer IG if exposed to infectious case within the last 2 weeks Exclusion from work / school Only if symptomatic

Infectious Period (green) If the 21st is the last day of exposure, the 4th is the last day you can give IG!! Sun Mon Tues Wed Thur Fri Sat 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21* 22 23 24 25 Onset 26 27 28 29 30 31 4 last day !

Control Measures (2) IG should be administered to all staff and attendees of a day care center or home if: 1 or more cases of Hepatitis A are recognized in children or employees or Cases are recognized in 2 or more households of center attendees

Control Measures (3) In day care centers that do not provide care to children in diapers, IG need be given only to classroom contacts of the index case-patient When an outbreak occurs (i.e hepatitis cases in three or more families of children in a day care center), IG should be considered for members of the households that have children (center attendees) in diapers

Control Measures (4) If a foodhandler is diagnosed with Hepatitis A: IG should be given to other foodhandlers at the same location Administration of Hepatitis A vaccine to other foodhandlers might also be considered IG administration to patrons may be considered if: the foodhandler directly handled uncooked foods or foods after cooking during the infectious period and had diarrhea or poor hygienic practices and patrons can be identified and treated within 2 weeks after exposure

Control Measures (5) Settings where repeated foodborne exposures to HAV may have occurred (i.e institutional cafeterias), stronger consideration of IG use may be warranted. Common source foodborne outbreak - IG should not be administered to exposed persons after cases have begun to occur because the 2 week period during which IG is effective will have been exceeded

Control Measures (6) Health care workers infected with HAV should be excluded from “hands on” patient care for 7 days following the onset of symptoms In a health care setting: Nosocomial transmission rare Use standard precautions (also use contact precautions for diapered or incontinent patients)

Example - Jo Husband = household contact + sexual contact; last contact during the infectious period 7 days ago => give IG Employed at a daycare. Attendees include infants and toddlers. => give IG to attendees and staff Made dinner for her mother-in-law 3 weeks ago during the infectious period; no contact since => no IG for mother-in-law Hospitalized – use standard precautions => no IG for hospital staff

Surveillance Investigation

Risk Factor Investigation of Hepatitis A Cases, West Virginia, 1999-2003; N = 198 Yes No Missing / Unknown Contact to a case of hep A? 52 (26%) 91 (46%) 55 (28%) Child or employee in daycare? 10 (5%) 171 (86%) 17 (9%) Household contact of child or employee in daycare? 13 (7%) 150 (76%) 35 (18%)

Risk Factor Investigation of Hepatitis A Cases, West Virginia, 1999-2003; N = 198 Yes No Missing / Unknown Foodhandler? 16 (8%) 166 (84%) … eat raw shellfish? 8 (4%) 147 (74%) 43 (22%) … travel outside the US? 4 (2%) 165 (83%) 29 (15%)

Surveillance Investigation Yellow card CDC hepatitis investigation form Laboratory slip, including ALT (SGOT), AST (SGPT), hepatitis serologies

In the 2 to 6 weeks prior to onset … Was the patient a contact of a person with hepatitis A? A child or employee in a daycare center…? A household contact of a child or employee in a daycare center …? How many (male/female) sexual contacts did the patient have?

In the 2 to 6 weeks prior to onset … Did the patient inject drugs not prescribed by a doctor? Did the patient use street drugs but not inject? Did the patient travel outside the US?

Investigation, continued Is the patient part of a common-source outbreak? Foodborne? Waterborne? Was the patient employed as a foodhandler in the two weeks prior to onset or while ill? Has the patient received the hepatitis A vaccine?

Hepatitis B Hepatitis B Vicki Hogan, MPH Epidemiologist HIV/AIDS and STD Program

Epidemiology Etiologic agent Reservoir— Small double stranded DNA virus The outer coat contains the Hep B surface antigen. Reservoir— only HUMANS.

Risk Factors Multiple sex partners or history of STDs Injecting drug users (sharing) Babies born to infected mothers Household members or sexual contacts Men who have sex with men Healthcare workers. Hepatitis B can affect any non-immunized person Household/sexual contacts of chronically infected persons Infants born to infected mothers Health care and public safety workers Persons with multiple sex partners or diagnosis of a sexually transmitted disease Men who have sex with men Injection drug users

Modes of Transmission Unprotected sex Mother to child Blood Injecting drugs Tattoo or body piercing with dirty tools Needle sticks (health care workers) Toothbrush or razor. HBV can survive outside the body at least 7 days and still be capable of transmitting infection.

Concentration of Hepatitis B Virus in Various Body Fluids Low/Not High Moderate Detectable blood serum semen urine wound exudates vaginal fluid feces saliva sweat tears breast milk

Acute Hepatitis B Surveillance Case Definition Clinical case definition An acute illness with discrete onset of symptoms and jaundice or elevated serum aminotransferase levels. Laboratory Criteria for Diagnosis IgM antibody to hepatitis B core antigen (anti-HBc) positive or hepatitis B surface antigen (HBsAg) positive IgM anti-HAV negative (if done).

Case Classification Confirmed Comments A case that meets the clinical case definition and is laboratory confirmed. Comments Persons who have chronic hepatitis or persons identified as HBsAg positive should not be reported as having acute hepatitis unless they have evidence of an acute illness compatible with viral hepatitis (with the exception of perinatal hepatitis B infection).

Symptoms of Acute Viral Hepatitis B The patient may have eyes or skin that has turned yellow have lost their appetite have nausea, vomiting, fever, stomach or joint pain feel extremely tired and not be able to work for weeks or months have dark urine and/or clay colored bowel movements. tiredness loss of appetite nausea abdominal discomfort dark urine clay-colored bowel movements yellowing of the skin and eyes (jaundice)

Chronic Hepatitis Lab criteria HBsAg (+) for > 6 months HBsAg + 2 times at least 6 months apart

Chronic Hepatitis Clinical criteria Usually asymptomatic May have fatigue, right upper quadrant discomfort End-stage liver disease may be the first sign Fever, worsening pain suggest: hepatocellular carcinoma / other complication ascites

Clinical Features Incubation Period: Range 45-180 days Average 60-90 days Infectious Period: Any person who is Acute illness HBsAg positive is Chronic potentially infectious Jaundice is age-dependent <10% of children less then 5 years of age 30% - 50% of older children & adults Most adults with acute HBV infections completely recover – clearance of HBsAg from blood & production of antibodies – immunity from further infections Chronic 30% – 90% of young children 2% – 10% of adults 15% – 25% of chronic people may die prematurely from either cirrhosis or liver cancer

Acute Hepatitis B Cases Reported to CDC in West Virginia from 1995 to 2003 (N=283) 60 53 50 43 36 36 40 30 29 Cases 26 30 16 20 14 10 1995 1996 1997 1998 1999 2000 2001 2002 2003 Year IDEP/DSDC/WVBPH/WVDHHR

Annual Average Incidence of Acute Hepatitis B in West Virginia by Age Group (1995-2003) (N=283) 5 4.5 4.5 4 3.5 3 3 2.5 Incidence 2 1.7 1.5 1 0.6 0.5 0.5 <1 1-4 yrs 5-14 yrs 15-24 yrs 25-39 yrs 40-64 yrs 65+ yrs Age group

Cure and Prevention of Hepatitis B Is there a “cure”? No, it is a virus Prevention through vaccination, education and changing behavior is important.

Prevention Measures Vaccination – The Best Prevention Education All high risk individuals Household contacts of chronic individual Children and adolescents Individuals who may be exposed to blood on the job Three doses are needed to complete the series. Education Patient, sex partners and household contacts

Prevention Measures Universal Precautions Needlestick injury Blood exposure Includes razors and toothbrushes

Post Exposure Prophylaxis Post exposure HBIG and vaccination Sex partners and household contactswithin 14 days Blood exposure within 7 days

Hepatitis B - Treatment Acute No specific treatment available. Chronic Adefovir dipivoxil Alpha Interferon Lamivudine Better tolerated than IFN-a

STD Investigations into Hepatitis B All hepatitis B activities are high priority assignments Positive HbsAg are received in the STD unit and assigned to staff within 24 hours

Role of DIS Local HD and DIS will work together to determine who will do follow up and to determine if this is a chronic or new case DIS will investigate sex partners, needle sharing partners and household contacts

Contact Investigation Status Sexual exposure within last 14 days Household exposure within 14 days Needle sharing exposure within 7 days Action Draw blood Give HBIG Start vaccine series

Websites WV HIV/AIDS/STD Program http://www.wvdhhr.org/bph/oehp/sdc/a-z/ a-z-hepatitis.asp National Viral Hepatitis Program http://www.cdc.gov/ncidod/diseases/ hepatitis/index.htm

Contact Information Vicki Hogan, MPH Epidemiologist vickihogan@wvdhhr.org HIV/AIDS & STD Program 350 Capitol St., Rm. 125 Charleston, WV 25301 (800) 642-8244 (304) 558-2950

Perinatal Hepatitis B Stephanie Moore, RN Perinatal Hepatitis B Coordinator Immunization Program

CDC Case Definition Clinical Case Definition: Perinatal Hepatitis B in the newborn may range from asymptomatic to fulminant hepatitis Laboratory criteria for diagnosis: Hepatitis B surface antigen (HBsAg) positive Case Classification: HBsAg positivity in any infant aged 1 to 24 months who was born in the US or in US territories to an HBsAg positive mother.

Risk Factors Mother who is HBsAg positive or whose status is unknown.

WV Statistics 37 birthing facilities Approximately 20,000 births a year 14 facilities with standing orders to vaccinate Percentages which is 38%

WV Statistics - Reporting 2001/ 2002/ 2003/ 2004 HBsAg + mothers 3 8 11 19 Great Improvement in reporting! Prior to mid 2003 all the report were submitted after the child was born – Now they are reported prior to birth : 2 points (improved awareness and Prenatal screening) Lag time was as far as 1 ½ yrs after to now 1-6 months prior to delivery.

WV Statistics - Deliveries Infants 2001 Deliveries 3 Received HBIG 3 100% Received Hep B (1) 3 100% Received Hep B (2) 3 100% Received Hep B (3) 3 100% Serology Testing 1 33% Infants born to HBsAg + mothers per each year and the following F/U Activities

WV Statistics - Deliveries Infants 2002 Deliveries 3 Received HBIG 3 100% Received Hep B (1) 3 100% Received Hep B (2) 3 100% Received Hep B (3) 2 66% Serology Testing 2 66%

WV Statistics - Deliveries Infants 2003 Deliveries 5 Received HBIG 2 40% Received Hep B (1) 4 80% Received Hep B (2) 3 60% Received Hep B (3) 1 20% Serology Testing n/a

WV Statistics - 2004 9 HBsAg + mothers to deliver this year

Transmission From mother to infant at birth

Infants born to mothers positive for (HBsAg) and (HBeAg) have a 70-90% chance of acquiring hepatitis infection, 85-90% will become chronic carriers in the absence of post exposure prophylaxis.

An estimated 15-25% of the carriers will ultimately die of liver failure secondary to chronic hepatitis, cirrhosis, or primary hepatocellular carcinoma.

Maternal Screening Advisory Committee on Immunization Practices, American College of Obstetrics and Gynecology, American Academy of Pediatrics recommend that all pregnant women be routinely screened for HBsAg during an early prenatal visit If a woman has not been screened prenatally, or the results are unavailable at the time of delivery, HBsAg testing should be done at admission of delivery

Before Birth Educate the mother about hepatitis B HBIG and hepatitis B vaccine should be available at the birthing facility prior to delivery The local health department should negotiate with physicians to assure that all of the following are followed:

Before Birth Physicians orders are written. A pediatric provider is identified. to assure that HBIG and the first dose of hepatitis B vaccine will be administered within 12 hours of birth of infant.

At Birth HBIG and the first dose of hepatitis B vaccine are given. Birthing facilities should notify the local health department when the child is born. HBIG and the first dose of hepatitis B vaccine are given. Premature infants born to HBsAg positive mothers should receive hepatitis B vaccine and HBIG at or shortly after birth. and the immunization record is reported to WVSIIS (West Virginia Statewide Immunization Information System)

After Birth Follow up to assure that the infant receives vaccination doses number 2 and 3 on schedule. Serology ( HBsAg and HBsAb) should be drawn 3 to 9 months after the third dose of hepatitis B vaccine (i.e. 9-15 months of age). and results reported to the Hepatitis B Coordinator Following the infant until the serology has been reported as positive or negative.

Serology Results If HBsAg is negative and HBsAb is positive = immunity. If HBsAg positive, refer to physician for follow-up care. If HBsAb and HBsAg are negative, repeat series.

Identify - Vaccinate - Follow - Test Prevention is the Key Identify - Vaccinate - Follow - Test

YOU can make the difference.

Websites WV Immunization Program http://www.wvdhhr.org/immunizations National Immunization Program http://www.cdc.gov/nip

Contact Information Stephanie Moore, RN Perinatal Hepatitis B Coordinator stephaniemoore@wvdhhr.org WV Immunization Program 350 Capitol St., Rm. 125 Charleston, WV 25301 (800) 642-3634 (304) 558-2188

I’VE GOT A RESULT… NOW ???? WHAT Dondeena McGraw Microbiologist III Leadworker Serology Section Office of Laboratory Services

Lab Requisition Form

“Serology” Terminology Screen HBsAg HBcAb (Tot) Post Vac HBsAb or anti-sAg OCME HBsAg (only) Hepatitis A virus HAV – Igm Hepatitis C virus Antibody

Hepatitis B Worksheet Screen Non- reactive Non-reactive Do Not Test HBsAg ANTI HBc ANTI HBs Hep B IgM Conf When to resubmit Screen Non- reactive Non-reactive Do Not Resubmit Reactive 4 weeks 6 months

If same results resubmit in 6 months Hepatitis B Worksheet Test HBsAg ANTI HBc ANTI HBs Hep B IgM Conf When to resubmit Screen Non-reactive Reactive DO NOT Resubmit 4 weeks If same results resubmit in 6 months

4 to 6 wks after last vaccine Hepatitis B Worksheet Test HBsAg ANTI HBc ANTI HBs Hep B IgM Conf When to resubmit Post Vac Reactive 4 to 6 wks after last vaccine Non-reactive

Hepatitis A Worksheet Test Hep A IgM When to resubmit HAV Non-Reactive DO NOT Resubmit Reactive

Hepatitis C Worksheet Test Hep C (HCV) When to resubmit HCV Non-reactive DO NOT Resubmit Reactive With a serum to cut off ratio (s/co) above 3.8 With a serum to cut off ratio (s/co) below 3.8 Resubmit in 4 weeks

As always…. No lab test is 100%, take into account patient history physical exam lab test results before final diagnosis for patient can be determined.

Contact Information Dondeena McGraw Microbiologist III Leadworker Serology Section Office of Laboratory Services 167 11th Avenue South Charleston, WV 25303 (304) 558-3530 ext 2405 or 2401

Whoaaaa…. Believe a Brief Intermission is Appropriate at this Stage…

Hepatitis C Thein Shwe, MS, MPH Hepatitis C Coordinator Infectious Disease Epidemiology Program

What is Hepatitis C Virus? a small, single-stranded RNA virus Member of the Flavivirus family 6 genotypes and many subtypes exist Discovered HCV by molecular cloning in 1988

Features of Hepatitis C Virus Infection Incubation period: Average 6-9 weeks (Range 2-26 weeks) Infectious period: from about 2 weeks after exposure for an indefinite period of time Persons with chronic hepatitis C – intermittently viremic Persons who test positive should be assumed to be infectious unless repeated testing for HCV RNA is documented to be negative.

Features of Hepatitis C Virus Infection (2) Acute Illness (jaundice) Mild (≤20%) Case fatality rate Low Chronic infection 55%-85% Chronic hepatitis (most asymptomatic) 70% Cirrhosis 5%-20% Mortality from Chronic Liver Disease of those with cirrhosis 1%-5%

Signs and Symptoms: Acute Viral Hepatitis Malaise, weakness, Anorexia, nausea, vomiting, vague but dull right upper quadrant pain Jaundice / dark urine Enlarged, tender liver Considerable variability in presentation Diagnosis by laboratory testing

Chronic Hepatitis C Factors Promoting Progression or Severity Age >40 years at the time of infection HIV co-infection Other Male gender Other chronic co-infections (e.g., HBV) Increased alcohol intake Role of moderate or light intake unclear

Hepatitis C Virus Infection, United States New infection per year 1985-89 242,000 2001 25,000 Deaths from acute liver failure Rare Persons ever infected (1.8%) 3.9 million (3.1-4.8)* Persons with chronic infection 2.7 million (2.4-3.0)* HCV-related chronic liver disease 40%-60% Deaths from chronic disease/year 8,000-10,000 *95% Confidence Interval

Risk Factors Associated With Acquiring HCV Infections, United States Transfusion, transplant from infectious donor Injection drug use Occupational blood exposure (needle sticks) Birth to an infected mother Infected sex partner Multiple heterosexual partners

Efficiency of HBV and HCV Transmission Exposure HBV HCV Transfusion ++++ ++++ Injection drug use ++++ ++++ Perinatal ++++ ++ Needlestick +++ + Sexual +++ + Mucous membrane ++ +/- Non-intact skin + +/- Intact skin - -

Relative Infectivity of HBV and HCV HBV HCV Titer/mL 108-9 105 Environmental stability ++++ +

Injection Drug Use and HCV Transmission Highly efficient Contamination of drug paraphernalia, not just needles and syringes Rapidly acquired after initiation Incidence 15% per year Prevalence 30% after 2-3 years; >50% after 5 years Four times more common than HIV

Occupational Transmission of HCV Inefficient by occupational exposures Average incidence 1.8% following needle stick from HCV-positive source 10 times lower than for HBV infection Associated with hollow-bore needles Case reports of transmission from blood splash to eyes; one from exposure to non-intact skin Prevalence 1-2% among health care workers Lower than adults in the general population

Perinatal Transmission of HCV Only from women HCV-RNA positive at delivery Average rate of infection 6% Higher (17%) if woman co-infected with HIV Role of viral titer unclear Possible association Internal fetal scalp monitoring Prolonged rupture of membranes No association Delivery method Breastfeeding

Sexual Transmission of HCV Occurs, but efficiency is low Rare between long-term steady partners Accounts for 15-20% of acute and chronic infections in the United States Sex is a common behavior Large chronic reservoir provides multiple opportunities for exposure to potentially infectious partners

HCV Related to Health Care Procedures, United States Recognized in context of outbreaks or case reports Chronic hemodialysis Hospital inpatient and clinic outpatient settings Private practice Home therapy Unsafe infection practices Reuse of same syringe and needle to administer meds to multiple patients Medication prep and blood sample handling in same area Contamination of multiple dose medication vials

HCV Transmission from Health Care Workers to Patients Rare Transmission rate low

Sources of Infection for Hepatitis C Previously Acquired (<1990s) Newly Acquired (1995-2000) Injection Drug Use 60% Injection Drug Use 68% Sexual 15% Transfusion 10% Unknown 9% Sexual 18% Unknown 10% Other 1%* Occupational 4% Other 1%* Occupational 4% * Other includes nosocomial, iatrogenic, perinatal Sources: Based on Sentinel Counties, NHANES III

Routine HCV Testing: Not Recommended Health-care, emergency medical, and public safety workers Pregnant women Household (nonsexual) contacts of HCV-Positive persons The general population MMWR Oct. 16, 1998/Vol. 47/No. RR-19

Children Born to HCV-Positive Women Should be tested for HCV infection Testing should be performed no sooner than age 12 months RT-PCR for HCV RNA may be performed Immunoglobulin (IG) and antiviral agents are not recommended for post exposure prophylaxis of infants born to HCV-positive women MMWR Oct. 16, 1998/Vol. 47/No. RR-19

Hepatitis C Testing Serologic Testing for Anti-HCV Enzyme Immunoassay (EIA) Chemiluminescence immunoassay (CIA) Recombinant Immunoblot Assay (RIBA) Nucleic Acid Testing for HCV-RNA Quantitative Qualitative MMWR Oct. 16, 1998/Vol.47/No. RR-19

HCV Testing (2) Serologic Assays Hepatitis C virus antibody (anti-HCV) EIA (enzyme immunoassay) Initial screening test Only tests currently approved by US FDA for HCV infection diagnosis Detect anti-HCV Do not distinguish between acute, chronic, or resolved infection MMWR Feb. 7, 2003, Vol.52/No. RR-3

HCV Testing (3) Anti-HCV Screening Assays 3 immunoassays One enhanced chemiluminescence immunoassay (CIA) (VITROS® Anti-HCV assay, Ortho-Clinical Diagnostics) 2 enzyme immunoassays (EIA) Abbott HCV EIA 2.0, Abbott Lab ORTHO® HCV Version 3.0 ELISA, Ortho-Clinical Diagnostics Use HCV-encoded recombinant antigens. MMWR Feb. 7, 2003, Vol.52/No. RR-3

Screening test: positive HCV Testing (4) Test Result Interpretation HCV EIA 2.0 HCV Version 3.0 ELISA Repeatedly reactive Screening test: positive CIAs (VITRO anti-HCV assay) reactive MMWR Feb. 7, 2003, Vol.52/No. RR-3

What is Signal to Cutoff Ratio? An enzyme immunoassay test is read on a spectrophotometer for light passing through a filter at a particular wavelength(nm). Positive results will show color at that wavelength causing light to be absorbed. The positive and negative control averages are used to calculate a cut off value (amount of light absorbed by the positives compared to that absorbed by the negatives). Any result above that cut off number is considered "positive" and any below is considered "negative". Usually numbers for individual patients are read by the spec in "optical density" values [i.e. the light absorbed by the patient specimen, compared to the light absorbed by a blank (no specimen)]. "Signal to cut off value" or any other term relating to the patient value compared to the cut off or negative controls, is the ratio of the O.D. to the cut off (or the negative controls). If an assay had a cut off of .05 O.D. and a patient had a reading of 1.5 O.D., that patient would have a S/C ratio of 30.

HCV Testing (5) Screening test – Signal to Cutoff Ratio For EIA 3.8 and above For CIA 8 and above Reflex Supplemental Testing

WV Office of Laboratory Services HCV Testing Guideline Testing for HCV is performed ONLY on high risk patients with following criteria:  injecting drug users hemophiliacs needle sticks/blood splash prostitutes multiple transfusions >5 units sexual contact with: known infected persons homosexual/bisexual multiple partners

WV Office of Laboratory Services HCV Testing Guideline (2) SPECIMEN SUBMISSION Serum is the required specimen for this test. Blood should be drawn before heparin therapy. Whole blood is acceptable, but hemolysis may occur upon prolonged delay in separating the serum. Avoid exposure of specimen to extremes of temperature. Forcing whole blood through a small bore needle too quickly also causes hemolysis. COMPLETE THE HISTORY FORM, providing all information requested. Print so that information is clearly legible.

WVDHHR Hepatitis C Lab Survey (June 2003) The primary goal to determine how many laboratories have adopted the recent CDC guidelines for hepatitis C testing (MMWR February 7, 2003, Vol. 52, No. RR-3). Result After only 4 months after the release of the CDC guideline 36% of the labs have already performing reflex supplemental testing without a physician order.

WVDHHR Hepatitis C Lab Survey (June 2003) Recommendations: Laboratories are encouraged to review and adopt the CDC “Guidelines for Laboratory Testing and Result Reporting of Antibody to Hepatitis C Virus”. The signal to cutoff ratio offers a simple and cost effective way of routinely confirming positive screen test. When submitting hepatitis C test results, please report the full name, date of birth, address of the patient, and the name and address of the ordering physician or health care provider on each report to the Infectious Disease Epidemiology Program (as required by 64CSR7-8.2.b.2.A and 64CSR7-8.2.b.2.G)

Estimated Costs of HCV Testing $5 Per sample for initial screening test $15 Per sample for those testing initially reactive and repeated in duplicate $65-158 Per sample tested with RIBA $50-$295 Per sample tested with a NAT MMWR Feb. 7, 2003, Vol.52/No. RR-3

HCV Supplemental Testing Serologic anti-HCV assay Recombinant Immunoblot Assay (RIBA) – (Chiron RIBA® HCV 3.0 SIA) High specificity - Results: positive, negative, or indeterminate can be performed on the same serum or plasma sample collected for the screenings anti-HCV assay MMWR Feb. 7, 2003, Vol.52/No. RR-3

HCV NAT Test HCV RNA (hepatitis C virus ribonucleic acid) Used as supplemental test for anti-HCV Used commonly in clinical practice for diagnosis of acute and chronic HCV infection and for evaluating and managing patients with chronic hepatitis C MMWR Feb. 7, 2003, Vol.52/No. RR-3

HCV NAT Test (2) Nucleic Acid Test (NAT) FDA-approved diagnostic, qualitative detection of HCV RNA using reverse transcriptase polymerase chain reaction (RT-PCR) amplification Requires serum or plasma sample be collected and handled in a manner suitable for NAT and testing be performed in a lab. MMWR Feb. 7, 2003, Vol.52/No. RR-3

NAT Test (3) Test/Type Application Comments Qualitative Tests RT-PCR amplification of HCV RNA by in-house or commercial assays (e.g., Amplicor HCV™ Detect Presence of circulating HCV RNA Monitor patients on antiviral therapy Detect virus as early as 1-2 wks. After exposure Detection of HCV RNA during course of infection might be intermittent; a single negative RT-PCR is not conclusive False-positive and false-negative results might occur Quantitative Tests RT-PCR amplification of HCV RNA by in-house or commercial assays (e.g., Amplicor HCV Monitor™ Determine concentration of HCV RNA Might be useful for assessing the likelihood of response to antiviral therapy Less sensitive than qualitative RT-PCR Should not be used to exclude the diagnosis of HCV infection or to determine treatment endpoint MMWR Oct. 16, 1998/Vol.47/No. RR-19

Liver Enzymes Alanine aminotransferase (ALT) or SGPT Aspartate aminotransferase (AST) or SGOT Result: --- IU/L (reference range – e.g., 0-40)

Hepatitis C Surveillance

Case Definition: Acute Hepatitis C Clinical case definition An acute illness with discrete onset of symptoms and jaundice or elevated serum aminotransferase levels Laboratory criteria for diagnosis Serum alanine aminotransferase levels greater than 7 times the upper limit of normal, and IgM anti-HAV negative, and IgM anti-HBc negative (if done) or HBsAg negative, and Antibody to hepatitis C virus (anti-HCV) positive, verified by an additional more specific assay

Case Definition: Acute Hepatitis C (2) Case classification Confirmed: A case that meets the clinical case definition and is laboratory confirmed. Comment Up to 20% of cases of acute hepatitis C will be anti-HCV negative when reported and will be classified as non-A, non-B hepatitis because some (5%-10%) have not yet seroconverted and others (5%-10%) remain negative even with prolonged follow-up. Available serologic tests for anti-HCV do not distinguish between acute and chronic or past infection. Thus, other causes of acute hepatitis should be excluded for anti-HCV positive patients who have an acute illness compatible with viral hepatitis.

Hepatitis C Virus Infection Chronic or Resolved (2002) Clinical description Most HCV-infected persons are asymptomatic. However, many have chronic liver disease, which can range from mild to severe including cirrhosis and liver cancer. Laboratory criteria Anti-HCV positive (repeat reactive) by EIA, verified by an additional more specific assay (e.g. RIBA for anti-HCV or nucleic acid testing for HCV RNA) OR Anti-HCV positive (repeat reactive) by EIA with a signal to cut-off ratio >3.8.

Hepatitis C Virus Infection, Chronic or Resolved (2) Case Classification Confirmed - a case that is laboratory confirmed. Probable. A case that is anti-HCV positive (repeat reactive) by EIA and has alanine aminotransferase (ALT or SGPT) values above the upper limit of normal, but the anti-HCV EIA result has not been verified by an additional more specific assay or the signal to cut-off ratio is unknown.

Estimate of the number of persons diagnosed annually Risk Factors Hepatitis C Registry Gives information on: Demographics Estimate of the number of persons diagnosed annually Can be used to determine: Risk Factors Access to care Quality of care Resource needs

Hepatitis C Registry What do you do when you have a lab report of hepatitis C? Send it to IDEP via fax 304-558-6335 or mail Include patient and physician’s contact information if available

Hepatitis C Education Physician Education Public Education http://www.cdc.gov/ncidod/diseases/hepatitis/c_training/edu/default.htm Public Education http://www.wvdhhr.org/bph/oehp/sdc/hep_c_public.htm

West Virginia HCV Data Acute Hep C Chronic Hep C

Risk factors for Acute Hepatitis C Cases from 1995-2002 in WV (N=143) Number(%) Missing Data Injection Drug Use 41(29) 29(20%) >1 sex partners 39(28) 61(43%) Needle stick 7(5) 54(39%) Dialysis 21(16%) Transfusion 13(9) 25(18%) Healthcare Worker 10(7) 23(16%)

Estimated Chronic Infection with Hepatitis Viruses among inmates and releasees – US, 1997 No. & % of Jail & Prison Inmates with Condition No. & % among Noninmate population with condition No. among total US population with condition No. of releasee with condition and as % of US population with condition Hep. B Virus 34,000 (2%) 1-1.25 million (0.5%) 1.036-1.29 million 155,000 (12-15%) Hep. C Virus 255,000 (15%) 2.7 million (1.3%) 2.97 million 1.16 million (39%) MMWR March 14, 2003 Vol. 52, No. RR-1

Medical Evaluation and Management for Chronic HCV Infection Assess for biochemical evidence of Chronic liver disease (CLD) Liver enzymes (ALT, AST) Assess for severity of disease and possible treatment, according to current practice guidelines Other laboratory studies Liver biopsy (not mandatory) Vaccinate against hepatitis A and hepatitis B Counsel to reduce further harm to liver Limit or abstain from alcohol

Therapy of Chronic Hepatitis C Widely Accepted Indications Age above 18 years old Persistent ALT elevations HCV-RNA positive Liver biopsy showing significant fibrosis No contraindications Source: AASLD Practice Guidelines Feb. 2004

Therapy of Chronic Hepatitis C Individualized Indications Children 3-17 years old Normal ALT levels Mild liver disease Relapsers Source: AASLD Practice Guidelines Feb. 2004

Currently Recommended Optimal Treatment for Chronic Hepatitis C Adults Pegylated interferon and ribavirin Genotype 1 responders treated for 48 weeks 50% sustained response Genotypes 2 and 3 receive 24 weeks 80% sustained response Children 3-17 years old Standard interferon and ribavirin Sustained response 35% for genotype 1 70% for genotype 2 and 3

Reduce or Eliminate Risks for Acquiring HCV Infection Screening and testing donors Virus inactivation of plasma-derived products Risk-reduction counseling and services Infection control practices

Preventing HCV Transmission Avoid Direct Exposure to Blood: Do not donate blood, body organs, other tissue or semen Do not share items that might have blood on them such as razor, toothbrush, home therapy e.g., needles Cover cuts and sores on the skin

Persons Using Injection Drugs Provide risk reduction counseling, education Stop using and injecting Refer to substance abuse treatment program If continuing to inject Never reuse or share syringes, needles, or drug preparation equipment Vaccinate against hepatitis B and hepatitis A Refer to community-based risk reduction programs

Mother-to-Infant Transmission of HCV Post exposure prophylaxis not available No need to avoid pregnancy or breastfeeding Consider bottle feeding if nipples cracked/bleeding No need to determine mode of delivery based on HCV infection status Test infants born to HCV (+) women Consider testing any children born since woman became infected Evaluate infected children for chronic liver disease

Sexual Transmission of HCV Persons with One Long-Term Steady Sex Partner: Do not need to change their sexual practices Should discuss with their partner Risk (low but not absent) of sexual transmission Need for counseling and testing of partner (may provide couple with reassurance) Some couples might decide to use barrier precautions to lower limited risk further

Sexual Transmission of HCV Persons with High-Risk Sexual Behaviors At risk for sexually transmitted diseases, e.g., HIV, HBV, gonorrhea, chlamydia, etc. Reduce risk Limit number of partners Use latex condoms Get vaccinated against hepatitis A & B

Post-Exposure Follow-Up of Workers For HCV infection Baseline testing of source for anti-HCV Person exposed to HCV-positive source, baseline and follow-up testing: anti-HCV and ALT, again at 4-6 months (or test for HCV RNA at 4-6 wks) Confirmation by supplemental anti-HCV testing of all positive by enzyme immunoassay IG not recommended; studies ongoing of early treatment of positives

Resources for Hepatitis C WVDHHR Hepatitis Information: http://www.wvdhhr.org/bph/oehp/sdc/a-z/a-z-hepatitis.asp CDC Hepatitis Information: http://www.cdc.gov/ncidod/diseases/hepatitis/ Coinfection with HIV and HCV: http://www.cdc.gov/hiv/pubs/facts/HIV-HCV_Coinfection.htm Guidelines for Laboratory Testing and Result Reporting of Antibody to Hepatitis C Virus: http://www.cdc.gov/mmwr/PDF/rr/rr5203.pdf Syringe Disinfection for Injection Drug Users http://www.cdc.gov/idu/facts/disinfection.htm Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Post-exposure Prophylaxis (MMWR, 6/29/01 Vol. 50(rr-11)) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5011a1.htm

Resources for Hepatitis C (2) Guidelines for Prevention and Control of Infections with Hepatitis Viruses in Correctional Settings: http://www.cdc.gov/mmwr/PDF/rr/rr5201.pdf Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease: http://www.cdc.gov/mmwr/preview/mmwrhtml/00055154.htm NIH Consensus Statement for the Management of Hepatitis C -2002: http://consensus.nih.gov/cons/116/116cdc_intro.htm HIV/HCV Coinfection Center for Excellence: http://www.uchsc.edu/mpaetc.coinfection/ Hepatitis C Connection: A Hepatitis C Network and Support System: http://www.hepc-connection.org

Hepatitis B and C Outbreak Morgan County, WV

Demographic Background

History of the Outbreak An acute Hepatitis B case was reported to Morgan CHD in August 2003 Identified another acute hepatitis B positive case diagnosed in June 2003 PHN and DIS investigated and identified IVDU related among these two cases Acute hepatitis C cases reported in Feb. 2004 Interviewed patient and identified many IVDU contacts related to 2003 acute hepatitis B cases

Outbreak Investigation Objective Identify the extent and characteristics of the outbreak Identify the risk factors of hepatitis B and C Implement the viral hepatitis B and C prevention and control to prevent additional cases

Outbreak Case Definition Hepatitis B A case that have clinical symptoms of viral hepatitis and/or laboratory confirmation of HBV serology: HBsAg positive and/or HBcIgM positive Hepatitis C A case that have clinical symptoms of viral hepatitis and/or laboratory confirmation of HCV serology: HCV AB with confirmatory test positive

Case Findings

Male 1 Female 1 Female 2 Female 3 Female 4 Male 2 Male 3 Male 4 Male 5 Acute Hep. B and HCV infection HAV (-) Female 1 Acute HBV HCV (-) Female 2 HBV (-) HCV(-) Female 3 Acute HBV, HCV(-) Female 4 HBV (-) HCV(-) Male 2 Acute HCV HBV(-) Male 3 HBV – UK HCV - UK Male 4 HBV(-) HCV (+) Male 5 Acute HCV HBV (-) Male 15 HBV & HCV (-) F6 Male 6 HBV (-) HCV (+) Female 10 HBV(-) HCV(-) Male 12 UK Male 11 HBV (-) HCV (-) Male 9 UK Male 7 HBV HCV (+) Female 11 HCV(-) Male 13 UK Male 8 ?HCV Female 7 HBV(-) HCV (-) Female 9 HBV (-) HCV(-) Female 5 HCV (+) HBV (-) F 16 HCV(-) Male 14 UK Female 15 HBV & HCV (-) Male 10 UK Female 8 UK Female 12 UK Male 16, HBV & HCV (-) Male 17 – UK Male 18 - UK Male 19 - UK Female 14 HBV & HCV (-) Female 13 HBV(-) HCV(-)

No Case ID Age Gender Onset Date Symp-toms Lab Test Diagnosis Contact Risk Factors Hep. B Vaccine 1 Male 1 (index case) 31 Male 6/20/03 Yes HBsAg(+), HCV Ab (+) Acute Hep B and Chronic Hep. C 4 sexual contacts, 4 needle sharing contacts IVDU, Multiple sexual partners 2 Female 1 25 Female 7/29/03 HBsAg(+) Acute hep. B One sexual contact Sexual contact 3 Female 3 30 8/8/03 Acute Hep. B 3 sexual contacts, 2 household contacts Multiple sex partners, household 4 Male 2 ? HCV Infection 3 needle sharing contacts, 4 household contacts, one sexual contact IVDU, sexual, household 5 Male 5 19 2/24/04 Acute Hep. C 6 needle sharing partners, one sex partner IVDU, sexual 6 Male 7 38 HCV AB (+) 2 sex partners Sexual 7 Male 4 (brother of male 6) 35 HCV Ab(+) Hepatitis C infection 2 needle sharing contacts, 3 sexual contacts 8 Male 6 (brother of male 4) 34 2 sexual contacts 9 Female 5 37 HCV PCR (+) since 2001 Chronic Hep. 3 household contacts, 2 sexual and needle sharing contacts

Descriptive Epidemiology Person Identified 9 cases, 6(67%)male and 3 female(33%) Mean age –31(range 19-38) Median age – 31 Race – all white (100%) Place: all cases live in Morgan County, Time: June 2003 to present (ongoing)

Risk Factors for Hepatitis B and C Cases No.(%) Injection Drug Use 7(78%) Sexual Contact 8(89%) Household 2(22%)

Prevention and Control Measures Provide testing and counseling for hepatitis B, hepatitis C and HIV infection Provide education on hepatitis B, hepatitis C and HIV Provide free condoms Provide Hepatitis B vaccines to those who are negative for HBV infection Provide referral to drug treatment centers for people who used drugs Provide medical referral for HCV and HBV infected patients

Hepatitis B and C Testing and Counseling Name of Test No. of test done No. of positive result HBsAg HBc AbTotal 16 0(0%) HCV AB with high s c/o ratio 22 7(32%) HIV 10

Challenges of Outbreak Investigation Lack of Resources Testing – HCV confirmatory test, liver function test Vaccinations for hepatitis A and B Reporting Not reporting acute hepatitis B from health care providers and health care facility Contact tracing Unable to contact Lack of manpower Case follow up Loss to follow up

Contact Information Thein Shwe, MS, MPH theinshwe@wvdhhr.org 350 Capitol St., Rm. 125 Charleston, WV 25301 (304) 558-6429

Job Well Done!!! Angel Bloom-McJilton John Gundling Tom Manjerovic Wile E. Coyote Award for Perseverance Presented to Angel Bloom-McJilton John Gundling Tom Manjerovic Kim Kline In Recognition of your Tireless and Ongoing Pursuit of Hepatitis B & C Outbreak Contacts, beep-beep, commencing in 2003 and continuing still!!! Job Well Done!!! August 2004