Question

Previous testing on a donor’s computer record indicates CMV antibody–negative. The most recent donation demonstrates that antibodies are currently present.

1. Can the donor still donate?

2. Why has the CMV antibody test result changed?

3. What patients require the transfusion of CMV-reduced-risk blood products?

4. What alternatives exist in the provision of CMV antibody–negative blood? (

Answer 1

1. Can the donor still donate?

Ans:-

CMV is so common that most of us have actually been exposed to the virus at some point in our lives ­the Center for Disease Control (CDC) estimates that between 50 and 80 per cent of people in the U.S. have had a CMV infection before age 40. But because it is harmless to healthy people with healthy immune systems, many people likely haven’t even realized it. The most common symptoms are cold and flu-like: fever, sore throat, fatigue, and swollen glands. These symptoms typically only last up to a few weeks and most often aren’t any cause for concern.

However, the virus is potentially dangerous to individuals who are immunocompromised due to organ transplants, HIV/AIDs infection, chemotherapy, or specific medications. The virus can also cause “severe disease” in infants who contracted the virus before birth…this type of CMV is called congenital CMV.

1 in 200 children is born with CMV, making it the most common virus that infants are born within the U.S. Congenital CMV can be passed to an infant if the mother is exposed to CMV, then the virus passes through the placenta to the fetus. Congenital CMV is the number one cause of non-genetic sensorineural hearing loss (SNHL) in children, and can also developmental disabilities, microcephaly, and in very rare cases, death.

However, there are steps you can take to try to prevent CMV infection. Many pregnant women including mothers, teachers, day-care workers, and nurses, contract CMV through contact with the body fluids of young children. So if you are pregnant or planning to become pregnant, here are a few methods you can use to help reduce your risk:

Do not share food, drinks, utensils, or straws

Do not put a pacifier in your mouth

Avoid contact with saliva when kissing a child

Do not share a toothbrush

Wash your hands, especially after

Wiping a child’s nose or mouth

Changing diapers

Feeding a child

Handling children’s toys

As with other viruses, once someone has had CMV, their body retains the antibodies. CMV is generally harmless to adults but can be fatal to babies. For this reason, babies needing transfusions as part of their medical care should only receive blood from donors who have not been exposed to CMV (CMV negative).

CMV is less commonly transmitted by receiving donated blood or organs from a person who is carrying CMV, or from donors who have acute CMV infection but are CMV IgG negative as they have not yet formed an immune response but have the circulating virus in their blood. CMV is generally harmless to adults but can be fatal to babies. For this reason, babies needing transfusions as part of their medical care should only receive blood from donors who have not been exposed to CMV (CMV negative). Regular testing is conducted on blood donations to check for CMV antibodies

So in that case patient should donate blood to an adult person only.

It is not on the 'official' STD list but it can be transmitted via unprotected sex. Cytomegalovirus (CMV) is a common virus that can infect anyone at any time. The majority of those who are infected do not realize it because symptoms are rare. ... There are thousands of viruses in our bodies.

Most CMV infections are "silent" and harmless, but in pregnant women, CMV can be transmitted to the fetus, with sometimes devastating effects to the unborn baby and newborn. Therefore, it is important if you are pregnant, or know someone who is pregnant, to be "CMV Aware" and "CMV Cautious"

Blood transfusion is usually a lifesaving therapeutic intervention. However, many preventable errors may make this a hazardous procedure ]. The World Health Organization (WHO) recommends that blood donation should in all cases be voluntary. However, in Nigeria, voluntary donors are relatively scarce. Hence, family replacement and commercial donors have become alternative sources of blood ]. Healthy persons who are between the ages of 18 and 65 years with haemoglobin (Hb) levels of not less than 13.5 g/dl in males or 12.5 g/dl in females are acceptable as donors if they test negative for transfusion-transmissible infections (TTIs). These TTIs include hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), malaria, syphilis and Chagas disease. However, females are only accepted as donors if they are not pregnant or breastfeeding. Human cytomegalovirus (CMV), otherwise called human herpesvirus type 5, over the years, has come to assume an important public health problem. As it is a significant cause of morbidity and mortality in pregnancy and among immunocompromised patients like recipients of organ transplants, HIV-infected persons, cancer patients on therapy and neonates

2. Why has the CMV antibody test result changed?

Ans:-  

Yes, it is possible

CMV IgM appears within the first 1 to 2 weeks after primary (new) infection; CMV IgG appears 1 to 2 weeks after IgM is detectable. IgG levels peak by 2 to 3 months post-infection and usually remain detectable for life.
IgM antibodies are produced by the body first in response to a CMV infection. They can be detected in the blood within a week or two after the initial exposure.
A positive result indicates a current or past CMV infection. A second blood test, called CMV IgM antibody will help determine if the CMV infection is current or past. If positive, the infection may be current, usually, sometime within the last 4 months, Positive CMV IgM results indicate a recent infection (primary, reactivation, or reinfection).
Positive CMV IgG results indicate past or recent CMV infection. These individuals may transmit CMV to susceptible individuals through blood and tissue products.

Laboratory Diagnosis of CMV Infection for Persons >12 Months

Serologic tests that detect CMV antibodies (IgM and IgG) are widely available from commercial laboratories. The enzyme-linked immunosorbent assay (ELISA) is the most common serologic test for measuring antibody to CMV.

• A positive test for CMV IgG indicates that a person was infected with CMV at some time during their life, but does not indicate when a person was infected. This applies for persons ≥12 months of age when maternal antibodies are no longer present.
• Measurement of CMV IgG in paired samples taken one to three months apart can be used to diagnose primary infection; seroconversion (1st sample IgG negative, 2nd sample IgG positive) is clear evidence for recent primary infection.
• The presence of CMV IgM cannot be used by itself to diagnose primary CMV infection because IgM can also be present during secondary CMV infection. IgM positive results in combination with low IgG avidity results are considered reliable evidence for primary infection, with limitations of avidity testing described below.

· IgG avidity assays measure the binding strength between IgG antibodies and virus that can help distinguish a primary CMV infection from a past infection. Following primary CMV infection, IgG antibodies have low binding strength (low avidity) then over 2-4 months mature to high binding strength (high avidity). Commercial tests for CMV avidity are available in the U.S. however they are not FDA-approved and require further standardization.

Laboratory Diagnosis of Congenital CMV Infection in Newborns

The standard laboratory test for diagnosing congenital CMV infection is polymerase chain reaction (PCR) on saliva, with urine usually collected and tested for confirmation. The reason for the confirmatory test on urine is that most CMV seropositive mothers shed CMV virus in their breast milk. This can cause a false-positive CMV result on saliva collected shortly after the baby has breastfed.
Specific steps for appropriate collection of saliva samples from a baby are as follows:
1. Collect a saliva specimen more than one hour after breastfeeding and within three weeks of birth, because detection of CMV after three weeks could be the result of post-partum infection.
2. Insert a sterile cotton or polyester swab into the baby’s mouth between the gum and cheek and swirl for several seconds.
3. Remove the swab and place into a buffer formulated for PCR diagnostic testing (several are available). If CMV is present, it will leach from swab to the liquid.
The liquid is processed according to the manufacturer’s instructions, and PCR testing is performed according to the protocol in the laboratory. Specific procedures and interpretation of tests vary according to the laboratory.
Currently, testing of newborns for CMV is not routinely performed, though some states perform targeted CMV testing of newborns who fail the hearing screening. CDC is currently studying whether dried blood spots (DBS), which are already collected on almost all newborns, can identify the majority of children most likely to suffer long-term health problems from congenital CMV.

3. What patients require the transfusion of CMV-reduced-risk blood products?

​​​​​​​Ans:-

Several transfusion strategies have been proposed to reduce the risk of TT-CMV in addition to leukoreduction:

• i) provision of seronegative blood products
• ii) provision of CMV DNA-negative blood products (NAT-negative products)
• iii) Provision of blood products from long-term seropositive donors

A recent study compared these strategies on the basis of the results for CMV DNA in whole blood samples from 22,904 donations. In this study, the classic strategy of seronegative blood products showed the lowest risk of transfusing cell-associated CMV. This effect was only significant, however, if even very low numbers of infected cells were taken into account. NAT-negative blood products showed the lowest risk for free CMV in plasma, but this difference reached significance only for comparison with CMV-untested donors. Blood products from long-term-seropositive donors contained potentially neutralizing antibodies against membrane proteins like gB, which might impair infection of at-risk patients by low concentrations of CMV.

Whole blood NAT testing would be an ideal option to detect both cell-associated and free CMV, but this approach is challenging, especially as a low limit of detection is required. To our knowledge, only plasma NAT, but not whole blood NAT, is used by some blood transfusion services.

To weigh the advantages and disadvantages of the alternative transfusion strategies, detailed knowledge would be necessary about the comparative infectivity of low concentrations of cell-associated versus free CMV, and the influence of neutralizing antibodies on the infectivity of low concentrations of CMV.

Until these facts are known, at least products from newly seropositive donors should be avoided for at-risk patients. This was also recommended in 2012 by the section ‘Safety of Blood Products’ of the German Society of Transfusion Medicine and Immunohematology. To reach this goal, all 3 above-mentioned strategies are suitable: provision of seronegative blood products, CMV-NAT-negative blood products, or blood products from long-term seropositive donors. In cases of suspected TT-CMV, both the serostatus of all implicated donors (seronegative, newly seropositive, long-term seropositive) and the CMV DNA concentration in stored plasma samples should be determined to gather further knowledge on which donors confer the lowest risk for TT-CMV.

Furthermore, conditions and duration of storage of blood products prior to transfusion could influence the stability of CMV. Therefore, the interval between blood donation and transfusion of the respective blood products should be investigated.

The risk of TT-CMV is low in high-risk CMVneg/neg HSCT patients transfused with leukoreduced blood products not tested for anti-CMV. The cause of anti-CMV IgG seroconversion is most likely passive antibody transmission by blood products. CMV seronegative products should be used for the following clinical indications: Pregnant women regardless of CMV status who require regular elective transfusions during pregnancy (but not during delivery); Recipients of intrauterine transfusions IUT; Neonates (up to 28 days post expected date of delivery)

4. What alternatives exist in the provision of CMV antibody-negative blood?

​​​​​​​Ans:-

Traditionally, leukoreduction and selection of blood products from seronegative donors have been used as alternative strategies to reduce the risk of transfusion-transmitted cytomegalovirus infections (TT-CMV) in at-risk patients. After the introduction of universal leukoreduction for red blood cell and platelet concentrates in Germany, a controversy evolved as to whether the additional selection of blood products from seronegative donors would reduce or even increase the risk of TT-CMV. The current knowledge about CMV infections in blood donors and the implications of this information on the effect of potential transfusion strategies. Even though there are conflicting data about the incidence of TT-CMV remaining after the introduction of leukodepletion, it has been clearly shown that both prevalence and concentration of CMV DNA in peripheral blood are highest in newly seropositive donors. Therefore, avoidance of blood products from these donors is the most important goal of any transfusion strategy.

This goal can be reached by:

i) Selection of blood products from seronegative donors

ii) Provision of CMV DNA-negative blood products

iii) Provision of blood from long-term seropositive donors.

In cases of suspected TT-CMV, all implicated donors should be investigated carefully to gather further knowledge on which donors confer the lowest risk for TT-CMV.