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    Detection Overview

    HIV/HCV detection: an overview (1), (2) 
        
    HIV and HCV are large epidemics that are spreading throughout the world.   Since the mode of spread is via blood and sexual contacts, one of the most important modes of curtailing the epidemic is good HIV and HCV diagnostics.

    This can ensure that no tainted blood units are used for transfusion, and when screening high-risk populations all those infected are detected, and thus treated and educated.

    Today, using standard serology tests, many infected individuals are missed, and thus more new infections, that could have been avoided, via direct education, happen daily.

    Due to the current limitations of the serology antibody tests some infectious blood units are transfused into needing individuals, spreading the infection even further.
    This is due to the “window period” of weeks, months and sometimes years from the time of HIV or HCV infection to the time of sero-conversion.

    The window period is due to suppression of the immune response against the virus.

    Current status of HIV and HCV Diagnostics.

    Tests for the detection of carriers are conducted all over the world.

    o The most common way to identify the carriers is by detecting the antibodies against the virus. 
    o Antibodies against HIV and HCV take weeks or months after infection to develop in the body.

    The infected yet sero-negative period is called the “window period”.

    Other tests are based on detecting the virus itself, by its proteins or its genetic material.

    HIV

    HIV (Human Immuno-deficiency Virus) is the virus that causes AIDS. In the initial period of the HIV infection the carrier is asymptomatic and thus does not know that he / she is infected. It takes years before AIDS develops. HIV is transmitted mainly by sexual contact, blood and blood products, and from mother to the fetus.

    The national blood banks test every blood donation for the presence of HIV, and these tests account for the largest portion of the HIV testing (~60% of the total tests carried out in the west). Currently the diagnosis of HIV is based on the detection of HIV antibodies in the serum.

    The time between exposure/infection and the detection of antibodies in the serum is called the “window period”. According to the CDC (Center for Disease Control), only 50% of those infected will seroconvert within 3 months of the exposure, and 95% will become seropositive within 6 months. Thus, HIV antibodies in the serum are often not detectable in the early stages of the infection, shortly after exposure, leaving infected units in the blood supply.

    Since the virus goes up in the blood some time before the antibodies appear, developing sensitive molecular biology techniques to detect the virus in the blood have been able to shorten the window period by 10-12 days.

    Since every day counts these methods have been introduced into the blood banks, as an additional screening tests for blood units, making every possible effort to make the blood supply as safe as possible. As sensitive as these methods and tests are, the weeks and months prior to this ‘rise in virus levels’, when the virus is not in the blood in measurable levels, are still left undetectable. It is this gap that still needs resolving

    An antibody enhancing method that enables the test to be positive throughout the whole infection period, is easy to perform and is relatively inexpensive could fill in the gaps.

    HCV:

    Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of persons who have this disease. HCV is spread by contact with the blood of an infected person. The hepatitis C virus (HCV) is one of the most significant health problems affecting the liver.

    More than 4 million Americans (1.3% of the U.S. population) and 170 million individuals in the world (3% worldwide) are infected with hepatitis C virus.

    The prevalence (number of cases in a population at a specific time) of hepatitis C virus infections varies in different parts of the world. For example, the prevalence of hepatitis C virus in Scandinavia is less than 0.5% of the population, whereas the prevalence in Egypt is over 20%. In the U.S. and Western Europe, the complications of hepatitis C virus chronic hepatitis and cirrhosis are the most common reasons for liver transplantation.(3)

    Usually people with HCV do not know they have the disease until the virus has already done some damage to the liver. This is one of the reasons that HCV advocate groups try to raise public awareness of this disease.(4)

    Some statistics and trends (5):

    o Number of new infections per year has declined from an average of 240,000 in the 1980s to about 30,000 in                  2003.

    o Most infections are due to illegal injection drug use. 

    o Transfusion-associated cases occurred prior to blood donor screening; now occurs in less than one per 2 million transfused units of blood. 

    o Estimated 3.9 million (1.8%) Americans have been infected with HCV, of whom 2.7 million are chronically infected. 

    o The risk for prenatal HCV transmission is about 4%.  o If coinfected with HIV the risk for prenatal infection is about 19%. 

    o A single positive PCR test indicates infection with HCV. A single negative test does not prove that a person is not infected. Virus may be present in the blood and just not found by PCR. When hepatitis C is suspected and PCR is negative, PCR should be repeated. 

    o HCV accounts for "most" liver transplants. 

    o Another reason for public awareness is that at least 4 million people in the United States presently have HCV.

     

     

     

     

     

     

     

     

     

    HCV detection methods (6)

    A number of diagnostic tests are currently available for hepatitis C virus.

    Screening tests:

    Screening tests are done to determine the presence of antibodies to hepatitis C virus in the blood. The enzyme immunosorbent assay (EIA) is the conventional, initial screening test to diagnose hepatitis C infection. The EIA measures specific antibodies to small pieces of the hepatitis C virus proteins (antigens). This test, therefore, is referred to as the anti-hepatitis C virus antibody test. Patients who have elevated liver enzymes (ALT/AST) and/or any of the risk factors for hepatitis C virus can be diagnosed to have hepatitis C virus with a greater than 95% certainty when the EIA is positive.

    On the other hand, certain patients whose immune systems are impaired (suppressed) may not have detectable anti-hepatitis C virus antibodies even if they are actually infected with hepatitis C virus. Such immune suppressed patients include those who are on renal dialysis, suffer from cancer and are receiving chemotherapy, or have active HIV infection. These patients cannot produce enough anti-hepatitis C virus antibodies necessary to generate a positive EIA test.

    When there is a low likelihood (risk) of hepatitis C infection, individuals who test positive for hepatitis C by EIA should undergo confirmatory testing using a specialized assay that likewise tests for antibodies against the hepatitis C virus proteins. This assay is called the Recombinant Immunoblot Assay(RIBA).Both the EIA and RIBA tests, however, do not distinguish among acute, chronic, and resolved hepatitis C virus infections because the anti-hepatitis C virus antibodies are in the blood in all three of these situations. Although EIA and RIBA are tests that measure antibodies against hepatitis C virus, these antibodies do not confer protection to the patient against acquiring hepatitis C virus. Rather, they only indicate exposure of the patient to the virus.


    The Importance of Early Detection.

    Early detection is cost effective to society both in terms of less “productive man-years” lost and in reduced health-care costs. Early detection leads to early treatment providing better chances to a better quality of life.
    The advantages are obvious and presented below. Advantages include:

    HIV:
           ·   Better and more complete detection of HIV exposure.                     
               This is important for the medical staff, life and health
               insurance companies, and for epidemiological studies.

            ·  Shorter anxiety period for the patient after a suspected                
               exposure to HIV.

            ·  Better options and possibilities for treatment (and even cure).

            .  Earlier diagnosis of HIV infection in pregnant women and         
               treatment with ART can prevent infection of the fetus/newborn.

            ·  Critical for planning experimental HIV vaccine and              
               prevention programs.

             · Detection and elimination of dangerous blood and
               blood products that cannot be detected by the       
               current tests due to the “window- period” (the time that lapses
              between exposure/infection with HIV and the                         
               appearance of HIV specific antibodies in the serum that can be
               detected by the current tests).

    HCV:
             ·  Better control of emerging epidemics.

             ·  Better and more complete detection of HCV exposure.
                This is important for the medical staff, life and health insurance
                companies, and for epidemiological studies.

             ·  An important tool in the discovery and development of drugs and
                vaccines for the specific infectious agents.

              ·  Detection and elimination of infected blood and blood products that
                 cannot be detected by the current tests.


    References:

    (1) Blood Safety in the Age of AIDSby Eric A. Feldman and Ronald Bayer
    (2) http://cira.med.yale.edu/
    (3) http://www.medicinenet.com/hepatitis_c/article.htm
    (4) www.hcvinfo.com
    (5) http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm
    (6) http://www.medicinenet.com/hepatitis_c/page6.htm

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

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