Prevalence of cytomegalovirus in paid and unpaid blood donor population in Tirana.
Abstract: Background

Cytomegalovirus (CMV) is one of the most transmitted infectious agents through blood transfusion. There were no reports on the prevalence of CMV in our donor population.

Aim

The aim of the study was to determine the epidemiology of CMV infection in blood donors and to compare the prevalence of CMV antibodies in paid and unpaid blood donors.

Materials and methods

The blood donor population was divided in paid blood donors (PBD, 1308) and unpaid blood donors (UBD, 415). Total CMV antibody assay results were analyzed and correlated with donor age, sex and socio-economic status in the whole donor population and in both groups.

Results

The CMV seroprevalence in blood donor population was 83%. The PBD showed significantly higher prevalence of total antibodies anti-CMV when compared with UBD, 92.9% vs. 51.8%.

Significant association of CMV seroprevalence with social class was noted, 88.3% "in low social class" towards 54.9%. The relationship between donor age and CMV status showed an increase in the percentage of seropositivity with age (65% in ages under 30 years old, 91.5% in ages more than 50 years old). The prevalence of the specific antibodies anti-CMV IgM was 5.5%.

Conclusions

This study showed that the population of blood donors is a population with high prevalence of CMV infection especially in PBD. Studies in patient populations are needed. Leucoreduction only might not be sufficient for all at risk patient populations.

Keywords: Cytomegalovirus, prevalence, blood donation, socioeconomic factors, population characteristics
Article Type: Report
Subject: Epidemiology (Social aspects)
Epidemiology (Health aspects)
Epidemiology (Analysis)
Immunoglobulins (Social aspects)
Immunoglobulins (Health aspects)
Immunoglobulins (Analysis)
Blood banks (Social aspects)
Blood banks (Health aspects)
Blood banks (Analysis)
Medical research (Social aspects)
Medical research (Health aspects)
Medical research (Analysis)
Medicine, Experimental (Social aspects)
Medicine, Experimental (Health aspects)
Medicine, Experimental (Analysis)
Infection (Social aspects)
Infection (Health aspects)
Infection (Analysis)
Prevalence studies (Epidemiology) (Social aspects)
Prevalence studies (Epidemiology) (Health aspects)
Prevalence studies (Epidemiology) (Analysis)
Authors: Seferi, Irena
Xhumari, Pal
Burazeri, Genc
Pub Date: 10/01/2009
Publication: Name: International Journal of Health Science Publisher: Renaissance Medical Publishing Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Renaissance Medical Publishing ISSN: 1791-4299
Issue: Date: Oct-Dec, 2009 Source Volume: 2 Source Issue: 4
Topic: Event Code: 290 Public affairs
Product: Product Code: 8093000 Blood Banks & Collection Centers; 8000200 Medical Research; 9105220 Health Research Programs; 8000240 Epilepsy & Muscle Disease R&D NAICS Code: 621991 Blood and Organ Banks; 54171 Research and Development in the Physical, Engineering, and Life Sciences; 92312 Administration of Public Health Programs SIC Code: 2836 Biological products exc. diagnostic; 8099 Health and allied services, not elsewhere classified
Accession Number: 221654547
Full Text: INTRODUCTION

Selection of cytomegalovirus (CMV)-seronegative blood is a recognized way of providing blood with a greatly reduced risk of CMV transmission. (1) This association has focused attention on the epidemiology of CMV infection in blood donor population.

Human CMV is a herpes virus which is present as a latent infection in a majority of population in many countries. It causes a potentially dangerous infection that may become fatal to immunocompromised patients. (2,3) Seropositivity differs in different parts of the world 40-100% (4,5,6) and is therefore very important to establish local epidemiology in order to assess the risk of CMV transmission through blood transfusion.

Primary CMV infection of CMV-seronegative patients can occur through transfusion of blood products from CMV-seropositive donors. In seropositive donors, latent CMV is found in peripheral blood monocytes (7), to a much lesser extent CMV exists as free virus in the plasma of window period donors. (8)

The prevalence of CMV in general population and among blood donors in Albania has not yet been documented. This work has been performed in order to determine the rate of seropositivity among blood donors in Albania, to compare the seropositivity among two groups of blood donors paid and unpaid and to use this data in developing proper strategies for reducing CMV infections through blood transfusion, especially in immunocompromised patients.

MATERIALS AND METHODS

National Blood Transfusion Centre in Tirana collects blood from two different groups of blood donors:

1--Paid blood donors

2--Unpaid blood donors which from their side are divided in:

a. Voluntary non remunerated blood donors

b. Family replacement donors

The population studied is the population of blood donors in Tirana during the years 2007-2008, divided as it is mentioned above in two groups of paid (1308) and unpaid (415) blood donors. Prevalence of anti-CMV is determined in total and divided according to age, sex, and social class in the blood donor population in general and also in each of the groups of donors. For determining the social class only the occupation of the donors was taken into account, and the donors were divided in workers/jobless (low/middle class) and intellectuals (high social class).

Serological tests

Serum from each donor was tested for total CMV antibody using the Abbott AxSYM System in which a micro particle enzyme immunoassay (MEIA) was utilized. Those resulted positive were further tested for anti-CMV IgM by the same method. Calibration procedures were performed and validated using positive and negative controls provided. Micro plates coated with human CMV strain (AD169) were incubated with test sera. After washing in Tris buffer, antihuman IgG conjugated with alkaline phosphatase was added, washed and reaction was probed with methylumbelliferyl phosphate. Positive and negative controls were provided and utilized for system calibration. Assay results less than 15 AU/ml were considered negative for IgG antibodies to CMV. Samples with results > 15 AU/ml were considered positive indicating the presence of past or current infection. The tests were performed and results were calculated according to the manufacturer's instructions. All samples were immediately separated on receipt and frozen at 30[degrees]C until tested. Thawing and freezing was kept to a minimum.

Statistical Analysis

The test [chi square] was used for studying the association between the prevalence of CMV and gender, age-group, social-class. When the p value was <0.05, this was considered as a statistically significant result. All the statistical analysis of the data was done with SPSS (Statistical Package for Social Sciences) version 10.0 (Chicago, Inc).

RESULTS

The overall prevalence of CMV in our population of blood donors was 83%. Prevalence of CMV in paid blood donors resulted significantly higher in comparison to the prevalence of CMV in unpaid blood donors (92.9% vs 51.8%, Tables I-III and Figures I,II). We also studied the relationship of the prevalence of CMV with the donor sex, age- group and social-class. The evaluation of the relationship between donor sex and CMV status showed no significant difference (83.5% in females vs 82.5% in males, Table IV).

For the statistical analysis, the donors were grouped in age-groups in intervals of 5 years except from 18-30 which were grouped as <30 years old, and 50-65 who were grouped as >50 years old, because of the small number of donors in comparison to other groups, as shown in Table V. The evaluation of CMV prevalence and age-group showed an increase of seropositivity with the age in the general donor population (65%-91.5%). In the population of paid blood donors a high prevalence of CMV is noted since in early ages <30 years old (94.1%) that increased with the age up to 96% in the age group >50.

The relationship between the social class and the CMV seropositivity is shown in Table VI. In the social class of workers/ jobless there was a significantly higher prevalence of seropositivity in comparison to the class of intellectuals (88.3% vs. 54.9%). The incidence of anti-CMV IgM was 5.5% (79 in 1430, Figure III).

DISCUSSION

The prevalence of CMV in our population of blood donors in general resulted in 83%. The prevalence in the unpaid blood donors was 51.8% whereas in the paid blood donor population was 92.9% (Tables I-III and Figures I,II). The results indicate prevalence statistically significant higher in paid blood donors than in unpaid blood donors. A higher prevalence of infectious agents in paid blood donors is reported from different studies. (9,10) If we refer also to the fact that 99,6% of paid blood donors in our study belong to the "low/middle social class", then a relationship also with this fact is found. This fact is confirmed also from other publications, where the prevalence of CMV is higher in the lower social class. (1,11)

The relationship between the social class and the prevalence of CMV in our study is shown in Table VI. For determining the social class in this study we were based only in the occupation, and it was noted a statistically significant higher prevalence of CMV in the "Low-middle social class" than in the "high social class". As mentioned above according to the occupation our donors were divided in intellectuals "high social class" and in worker/jobless "low-middle social class". This division of social class based on the employment alone is referred also from other publications (1) but is very important to mention that employment is not the only parameter taken into account when you divide the social class, but also the social-economic and cultural components are very important.

No association was found between CMV seropositivity and donor sex Table IV. This is similar to the findings of other authors. (12) CMV seropositivity increases with age. This finding is in agreement also with other authors. (1,13) In our study, the seropositivity increases with the age of the donors (from 65% in the ages under 30 years old, to 91.5% in the ages over 50 years old, Table V). This local information is very important because if we select younger donors we can have more donations CMV neg. So if seroprevalence of CMV in the whole donor population was 83%, in the ages <30 years old was 65% and even more if we select the unpaid blood donors <30 years old the prevalence decreases to 27.5%. More efforts should be directed towards recruitment of unpaid blood donors, where the prevalence of CMV but also other infections is lower than in paid blood donors. (9,10) Prevalence of specific anti-CMV antibodies IgM resulted in 5,5% (79 from 1430, Figure III). In the literature, we find prevalence of IgM specific that varies 1-13%.14,15 No association was found between levels of IgM and total CMV antibody.

According to this data, the prevalence of CMV is very high in our blood donor population. The impact of this high prevalence of CMV in the "high risk" patient population is still not studied and reported, but it is sure that with this high prevalence of CMV in blood donor population, an urgent intervention is needed for preventing transfusion-transmitted CMV (TT-CMV) for patient at high risk for this disease. Since latent CMV is found in peripheral blood monocytes (7), there are a lot of studies that refer a decrease in the transmission of CMV by leukoreduction of blood components. (16, 17) Therefore, the interventions could be "universal leukoreduction of blood components" and of course "screening of all blood units for CMV" or both. The coming year we are going to begin with universal prestorage leukoreduction, because this has come as a necessity. First of all, for preventing TT- CMV, based on the data of this study, but also for preventing febrile non-hemolytic transfusion reactions in multi-transfused patient populations (major beta thalassemia patients). The question is if leukoreduction only is enough in preventing TT-CMV for patients with high risk. From the literature, there are a lot of studies, which show that TT-CMV has occurred after leukoreduction. (18,19,20) The residual risk of leukoreduction only, versus CMV seronegative units only, has been 2.73% vs. 1.45% respectively (21) and there are no studies until now that compare seronegative/leukoreduced versus leukoreduced only blood components. Therefore, in many countries e.g. Ireland and the UK where universal leucoreduction has been introduced, patients who require CMV 'safe' products are receiving both CMV seronegative and leucoreduced blood components. This is shown also from the meta-analysis conducted from Vamvakas EC (21) who concludes that seronegative/ leukoreduced give the level of protection needed and should be used in preference to CMV-unscreened/leukoreduced components for patients of SCT (stem cell transplantation) setting, seronegative pregnant women and intrauterine fetal transfusions who are the patients at the highest risk for TT-CMV disease.

[FIGURE I OMITTED]

[FIGURE II OMITTED]

Since about 83% of blood donors in our country are seropositive for CMV, it would be very useful to screen all blood donors for CMV, to identify the CMV-seronegative blood donors and maintain an inventory of them for use as donors for immuno-suppressed individuals that belong to the highest risk groups (SCT patients, seronegative pregnant women and intrauterine fetal transfusions), whereas for other patient populations (preterm infants, cancer patients, HIV infected patients etc) we might go on only with leukoreduction, because the use of seronegative/leukoreduced blood components in all patient populations at risk for TT-CMV will imply an important change in blood banking practice in Tirana with significant financial implications.

CONCLUSION

The general observation of this study is that our donor population has a high prevalence of CMV antibodies, in this situation developing and maintaining an inventory of CMV-seronegative blood donors might be the right solution for selected at the highest risk patient population. Studies should be done also in patient populations in order to assess the impact of this high prevalence of CMV in blood donors.

More efforts should be directed towards recruitment of unpaid blood donors as a safer population of donors not only for CMV infection but also for other infections. Relationship between CMV seroprevalence and donor sex, age and social class resulted in our study as reported before in the literature.

Conflict of interest: None declared.

REFERENCES

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(4.) De Ory Manchon F, Sanz Moreno JC, Castaneda Lopez R, Ramirez Fernandez R, Leon Rega P, Pachon del Amo I. Human cytomegalovirus seroepidemiology in the community of Madrid. Rev Esp Salud Publica 2001;75:55-62.

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(12.) Zhang L, Hanff P, Rutherford C, Churchill C, Crumpacker C. Detection of human cytomegalovirus DNA, RNA and antibody in normal donor blood. J infectious Diseases 1995;171:1002-1006.

(13.) Gunther KC, Luban NLC. Transfusion transmitted cytomegalovirus and Epstein-Barr virus diseases. In: Rossi EC, Simon TL, Moss GS, Gould SA, editors. Principles of Transfusion Medicine. Baltimore: Williams and Wilkins, 1996.

(14.) Beneke JS, Tegtmeier GE, Alter HJ, Luetkemeyer RB, Solomon R, Bayer WL. Relation of titers of antibodies to CMV in blood donors to the transmission of cytomegalovirus infection. J Infect Dis 1984; 150: 883-888.

(15.) Lentz EB, Dock NL, McMahon CA. Detection of antibody to cytomegalovirus induced early antigens and comparison with for serologic assays and presence of viruria in blood donors. J Clinical Microbiology 1998;26:133-135.

(16.) Laupacis A, Brown J, Costello B, Delage G, Freedman J, Hume H, et al. Prevention of post-transfusion CMV in the era of universal leukoreduction: A consensus statement. Transfusion 2001; 41: 560-569.

(17.) Ljungman P. Risk of cytomegalovirus transmission by blood products to immunocompromised patients and means for reduction. Br J Haematol 2004;125:107-116.

(18.) Nichols WG, Price TH, Gooley T, Corey L, Boeckh M. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood 2003; 101:4195-4200.

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(21.) Vamvakas E. Is white cell reduction equivalent to antibody screening in preventing transmission of cytomegalovirus by transfusion. A review of the literature and meta-analysis. Transfus Med. Rev 2005; 19: 181-199.

Irena Seferi [1], Pal Xhumari [2], Genc Burazeri [3]

[1] National Blood transfusion Centre of Tirana, Albania

[2] Department of Haematology, University Hospital of Tirana, Albania

[3] Department of Public Health, University Hospital of Tirana, Albania

Corresponding author: Irena Seferi, NBTC, Tirana, Rruga Lord Bajron, Lapraka, Albania Telephone number: +355 4 2389901, +355682000124 Email: iqendro@yahoo.com.
Table I. CMV prevalence in the general donor
population (paid and unpaid donors)

          Number     Percentage

No          293         17.0
Yes        1430         83.0
Total      1723        100.0

Table II. CMV prevalence in unpaid donors

          Number     Percentage

No         200          48.2
Yes        215          51.8
Total      415         100.0

Table III. CMV prevalence in paid blood donors

          Number     Percentage

No           93          7.1
Yes        1215         92.9
Total      1308        100.0

Table IV. CMV prevalence in  general population
(paid andu npaidd onors) according to donor sex

                       Donor sex        Total

                  Femal       Male

CMV       No       136        157        293
                  16.5%      17.5%      17.0%

          Yes      689        741        1430
                  83.5%      82.5%      83.0%

Total              825        898        1723
                  100.0%     100.0%     100.0%

Table V. CMV prevalence in the general population
(paid and unpaid) according to age-group

                                   Age-group

              <30      31-35    36-40    41-45    46-50    >50

CMV     No    105      47       52       39       31       19
              35.0%    16.4%    15.3%    12.3%    12.4%    8.5%

        Yes   195      240      288      278      220      206
              65.0%    83.6%    84.7%    87.7%    87.6%    91.5%

Total         300      287      340      317      251      225
              100.0%   100.0%   100.0%   100.0%   100.0%   100.0%

Table VI. CMV prevalence in general population of
donors (paid and unpaid) according to social class

                       Social class

                  Low/Middle      High

CMV       No         170          123
                    11.7%        45.1%

          Yes        1280         150
                    88.3%        54.9%

Total                1450         273
                    100.0%       100.0%

Figure III. Prevalence of IgM specific

IgM specific

Yes      79
No     1351

Note: Table made from bar graph.
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