Current screening strategies for blood donor screening in developing countries
Marion Vermeulen, Constantia Boulevard, Constantia Kloof, Roodepoort, South Africa, 1715
Background The entire African continents counties are classified as developing countries according to the World Bank criteria. It is ironic that poverty is a cause of endemic disease which in turn is a cause of poverty. It has been described in the 2008 UNAIDS report that sub-Saharan Africa remains the region most heavily affected by HIV, accounting for 67% of all people living with HIV and 75% of all AIDS deaths in 2007 and in this environment millions of units of blood are collected.
Aims The aim of this review is to discuss the various different screening strategies of blood donations used in developing countries and to highlight some of the advantages and disadvantages.
Material & Methods This paper is based on a review of the literature as well as information provided by various transfusion services in Africa.
Results There are various systems for the provision of blood, the hospital based systems which consist mainly of transfusion units attached to laboratories at the hospital, most of which use donor replacement schemes or the more centralized transfusion centers that usually have a system for voluntary non remunerated altruistic donors. Currently most countries have a hybrid of these two systems with 70% of the blood coming from donor replacement schemes.
A range of screening strategies are used in Africa and it was estimated in 2004 that only 80% of the blood was screened for Transfusion Transmissible infections (TTI’s). One hundred and fifty five countries reported to the WHO global database that 100% screening was performed but of these only 71 were performed in a quality assured manner. Various assay systems with differing sensitivities and specificities are used. A rapid assay is performed prior to donation in some settings which has advantages and disadvantages. Studies have shown that performing two different rapid assays in serial or parallel is more sensitive than as a single test but may not be feasible in resource limited settings. The majority of African countries test using an ELISA method which is the recommendation of the WHO. Many creative studies have been performed to try and make the screening as cost effective as possible without too much loss in sensitivity. One such study showed that if a serial testing algorithm was used that tested HBsAg first and then HIV on the seronegative donations and then syphilis on the subsequent seronegative donations and finally HCV the costs per annum in screening could be reduced by €90 860 per annum in Ghana. The final screening strategy that is used in some developing countries is Nucleic acid testing (NAT), this strategy is used in South Africa, Namibia, Egypt and Ghana. Although this strategy increases the safety of the blood supply it has been shown that in some settings it is not cost effective and should be clearly investigated prior to implementation
Conclusion There are various screening strategies in Africa and due to a large amount of work performed by different organizations the plan is to have 100% voluntary blood donors and 100% screening by 2012. To do this a National blood screening programme and budgeting nationally for blood will be required.
For operational and analytical purposes, the World Bank’s main criterion for classifying economies is gross national income (GNI) per capita. Based on its GNI per capita, every economy is classified as low income, middle income or high income. Low-income and middle-income economies are sometimes referred to as developing economies. The groups are as follows: low income, $975 or less; lower middle income, $976–$3855; upper middle income, $3856–$11 905; and high income, $11 906 or more. All of the African countries fall into the first three groups and hence are referred to as developing countries ranging from Zimbabwe being ranked the lowest in the world and South Africa being ranked the highest in Africa but only 29th in the world .
Developing countries such as those found in the continents Africa and Asia are caught in a vicious cycle of poverty and epidemic of disease and each causes the other to occur. These countries have been affected with the highest burden of the human immunodeficiency virus (HIV) as well as the hepatitis B virus (HBV). In the year 2009 UNAIDS report, it has been described that sub-Saharan Africa remains the region most heavily affected by HIV, accounting for 67% of all people living with HIV and for 75% of AIDS deaths in 2007. Sub-Saharan Africa’s epidemics vary significantly from country to country in both scale and scope. Adult national HIV prevalence is below 2% in several countries of West and Central Africa, as well as in the horn of Africa, but in 2007 it exceeded 15% in seven southern African countries (Botswana, Lesotho, Namibia, South Africa, Swaziland, Zambia, and Zimbabwe) and was above 5% in seven other countries, mostly in Central and East Africa (Cameroon, the Central African Republic, Gabon, Malawi, Mozambique, Uganda, and the United Republic of Tanzania) . It was in the southern African countries most heavily affected by disease that HIV has reduced life expectancy by more than 20 years, slowed economic growth and deepened household poverty. In sub-Saharan Africa alone, the epidemic has orphaned nearly 12 million children aged less than 18 . The natural age distribution in many national populations in sub-Saharan Africa has been dramatically skewed by HIV, with potentially perilous consequences for the transfer of knowledge and values from one generation to the next. In Asia, where infection rates are much lower than in Africa with 4·7 million people infected in 2008 and the incidence of new infections decreasing on an annual basis since 1990, HIV causes a greater loss of productivity than any other disease and is likely to push an additional 6 million households into poverty by 2015 unless national responses are strengthened . It is in this environment that the blood transfusion services in developing countries collect 39% of the worlds blood supply from 82% of the world’s population [3–5]. The provision and concomitant safety of blood transfusion are liberally assumed in the developed world; in contrast, limited access to blood transfusion or provision of unsafe blood renders blood safety a major public health concern in the developing world. Currently, 3 million units of blood is collected annually in Africa which is 58·6% short of the required amount . In Asia 9·4 million units of blood is collected annually, 41·25% below the required amount . It has been estimated that between 5 and 10% of HIV transmission in Africa is through unsafe blood transfusion, with 25% of maternal and 15% of childhood deaths, partially caused by blood transfusion not being available when required . In Africa and Asia there are various systems for the provision of blood, the hospital-based systems which consist mainly of transfusion units attached to the main laboratories of a hospital, most of which use donor replacement schemes or the more centralized transfusion centres that usually have a system for pre donation counselling and voluntary non-remunerated blood donors (VNRBD). Currently many countries have a hybrid of the two systems with approximately 75–80% and 33% of the blood coming from replacement donors in Africa and Asia, respectively [6,8]. The establishment of systems to ensure that all donated blood is screened for transfusion-transmissible infections is a core component of every blood programme. Globally, however, there are significant variations in the extent to which donated blood is screened, the screening strategies adopted and the overall quality and effectiveness of the blood screening process. In 1991, the World Health Organization Global Programme on AIDS and then the League of Red Cross and Red Crescent Societies published Consensus Statement on Screening Blood Donations for Infectious Agents through Blood Transfusion. Since then, there have been major developments in screening for transfusion transmissible infections, with the identification of new infectious agents and significant improvements in the detection of markers of infection in donated blood .
It should be recognized, however, that all blood screening programmes have limitations and that absolute safety, in terms of freedom from infection risk, cannot be guaranteed. In addition, each country has to address specific issues or constraints that influence the safety of its blood supply, including the incidence and prevalence of blood-borne infections, the structure and level of development of the blood transfusion service, the resources available and special transfusion requirements. This article is based on the WHO recommendations for screening strategies in developing countries, a literature review of current practices and information supplied from many countries in Africa for which I am very thankful to the Safe Blood for Africa Foundation (SBFA) in assisting with providing sources from which to obtain data for individual countries.
From the outset it was noticeable that information supplied and found in the literature differed from the information found in the WHO global report. This could be, and I hope is, because of a concerted effort by African countries to meet the goals set out by WHO in 2006. The challenges that face transfusion services in developing countries are very different from the challenges of developed countries. A main challenge facing developing countries is the lack of a national programme for blood transfusion. In 2006, the WHO African region with 46 member states and the WHO Asia region with 11 member states only had eight and six countries respectively that have a national blood programme [1,6]; however, the development and implementation of the PEPFAR initiative by AABB, SBFA, WHO and Sanguin are increasing these numbers in Africa. At national level, the main challenges are often ineffective policies, lack of national standards or screening strategies, and limited resources for implementing the national blood screening programme. Many governments do not budget nationally for blood or blood products but leave the responsibility of recruiting, testing and processing of blood donations to the hospitals. At the operational level, the effectiveness of blood screening is often constrained by the fragmentation and lack of co-ordination of blood transfusion services, inadequate infrastructures, shortages of trained staff and poor quality systems. The first line of defence in providing a safe blood supply and minimizing the risk of transfusion-transmitted infection depends on the source, the safest source, according to WHO, is to collect blood from well-selected, voluntary non-remunerated blood donors (VNRBD) from low-risk populations, particularly those who donate regularly. The prevalence of TTIs in voluntary non-remunerated blood donors is generally much lower than among family/replacement and paid donors [9–11]; however, in a study in Ghana it was found that the difference in prevalence is not attributed to the motivation of the donor but rather to whether the donor is a first-time donor or repeat donor and showed that first-time replacement donors had a similar prevalence to first-time voluntary donors . When the government is not supplying financial resources to procure blood, the easiest and the cheapest method of obtaining sufficient blood is to use family replacement donations, and these donations cost approximately 2–3 times less than VNRBD . Another challenge is that a significant proportion of donated blood remains unsafe as it is either not screened for all the major TTIs or is not screened within a quality system (Table 1). Data on blood safety indicators provided in 2006 by ministries of health to the WHO Global Database on Blood Safety (GDBS) indicate that 95% of African countries were testing 100% of units for HIV, 83% of countries were testing for HBV and 53% for HCV, the plan is to have 100% of the blood screened by 2012 for all of these TTI markers . Of the 155 countries that reported performing 100% screening for HIV, only 71 screen in a quality-assured manner which is defined as screening performed in blood centres/blood screening laboratories that (i) follow documented standard operating procedures and (ii) participate in an external quality assessment scheme. In Asia all blood is 100% tested for HIV and HBV except in Indonesia which tests 97%; however, HCV testing has not been initiated in all countries yet . Gabon also tests for HTLV I/II. Various assay systems with differing sensitivities and specificities are available for blood screening. However, the efficacy of screening depends on their correct use in laboratories that are appropriately resourced and staffed and that have well-maintained quality systems.
Table 1. Number of countries testing 100% for TTI
The WHO recommends the efficient co-ordination of blood transfusion services at national level as a prerequisite for an effective and sustainable national blood screening programme. Co-ordination is essential to maintain continuity in operations and consistency in performance in all facilities in which screening is performed, including blood centres and hospital-based services. Each screening facility requires a specific and sufficient budget, a suitable infrastructure, with reliable water and power supplies, well-maintained equipment and efficient transportation and telecommunications systems. Greater efficiency and safety can be achieved by bringing together key blood screening activities into a network of strategically located central and/or regional blood centres with well-trained staff, suitable equipment and efficient procurement and supply systems. By facilitating economies of scale, this enables overall costs to be minimized without compromising quality . Conversely, the screening of blood in multiple small centres usually leads to the wastage of precious resources and a lack of uniform standards. In countries with hospital-based blood services, national health authorities should assess the need and feasibility of consolidating screening activities at national and/or regional levels so that the national screening programme can be implemented more efficiently and cost-effectively.
With regards to the testing, it is important that the resources are used wisely and not wasted unnecessarily. The national blood screening strategy should be reviewed periodically to determine whether there is a need for any amendment because of new evidence or changes in the epidemiology of infection in the general population. In the context of blood screening, appropriate evaluation is required in selecting the type of assay for each TTI, based on critical assay characteristics, such as sensitivity and specificity, as well as cost and ease of use. Although NAT reduces the window period of infection, in countries with a low incidence of infection, the incremental gain is minimal as the number of donors in the window period at the point of donation is generally very low. However, in countries with a high incidence of infection there are likely to be significant numbers of window period donations that can be identified by NAT. Thus, although the risk of transfusing a blood unit collected during the window period may be decreased using NAT, the actual benefit in most populations has first to be determined and should be balanced against the complexity and high cost of performing NAT, including the infrastructure required. For countries with sufficient resources, NAT offers certain benefits. However, the potential benefit of detecting early infections and preventing possible transmissions of infection should be assessed in relation to such factors as the incidence and prevalence of infection in the blood donor population, the effectiveness of the blood donor selection process, the sensitivity of the serological screening currently undertaken and the ability to enhance this through, for example, the use of more sensitive serological assays such as combination antigen–antibody assays .
Currently, there are a variety of screening strategies used in developing countries. This ranges from the least favourable for sensitivity whereby a rapid test is performed to screen donors, any positive results and the donor is counselled and blood is not taken. Rapid tests are provided in simple-to-use formats that generally require no additional reagents except those supplied in the test kit. They are read visually and give a simple qualitative result within minutes. There are many disadvantages such as the reading of results being dependent on subjective evaluation, a lack of any permanent record of the original test results and a lack of sensitivity. This is compounded by the inability to apply acceptable quality systems effectively to such tests. Rapid tests are generally not suitable for screening large numbers of blood samples. The advantages, though, are that in small rural blood hospitals when blood is donated a rapid test can be performed when required without requiring expensive equipment. If the test result is positive, the blood unit is not drawn and hence the blood bag costs are saved [13,14]. The donor can be counselled immediately and so the risk of not being able to track down the donor later for counselling is also avoided. In Tanzania five rapid assays were evaluated against the inno Lia confirmatory assay to determine the highest sensitivity model for use and the authors recommended using a combination of Determine™ HIV-1/2 (Inverness Medical Japan Co. Ltd, Tokyo, Japan), SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc., Kyonggi-do, Korea) and Uni-Gold™ HIV-1/2 (Trinity Biotech, Wicklow, Ireland) to screen and confirm was 100% sensitive and cost-effective in their high prevalent population  in another study in cost-effectiveness using rapid assay strategies it was noted that a serial or parallel strategy using rapid assays was more sensitive than a single use rapid assay but that in certain resource limited settings may not be a cost-effective choice and that each clinical setting should determine its own algorithms . The recommended WHO screening strategy, the most common strategy, is to use enzyme and chemiluminescent immunoassays for screening donated blood for TTIs. The design of EIAs and CLIAs is similar and they differ only in the mode of detection of immune complexes formed – colour generation in EIAs and measuring light produced by a chemical reaction in CLIAs. Any of these types of immunoassays with high sensitivity will generally detect the target markers of infection required if they have been properly evaluated for blood screening and are then used within a quality environment. EIAs and CLIAs are suitable for the screening of large numbers of samples and require a range of specific equipment. These assays may be performed either manually or on non-dedicated automated assay processing systems (open system). They may also be manufactured specifically to operate on specific dedicated automated systems (closed system). The disadvantages of these methods are the skills and competence required by the staff. If these tests are not performed in a quality system, then any initial reactive is usually destroyed but if a quality system is in place the tests can be repeated in duplicate and only if the sample is repeatedly reactive is the donation discarded. NAT, as applied to blood screening, detects the presence of viral nucleic acid, DNA or RNA, in donation samples. In this technology, a specific RNA/DNA segment of the virus is targeted and amplified in-vitro. The amplification step enables the detection of low levels of virus in the original sample by increasing the amount of specific target present to a level that is easily detectable. The presence of specific nucleic acid indicates the presence of the virus itself and that the donation is likely to be infectious. NAT assays can either be performed on individual donations (ID) or on mini-pools (MP) to detect the nucleic acid of the infectious agent. In addition to NAT assays which target individual viral nucleic acids, multiplex NAT screening assays have been developed which can detect DNA or RNA from multiple viruses simultaneously. Currently, South Africa, Namibia, Egypt and in some areas in Ghana have implemented NAT. South Africa has been unfortunate in regard to the AIDS burden that the country carries. It has a prevalence of 18% in the general population, of which the large majority of disease is from the ages of 16 to 60 the same age group that a blood service collects blood from. However, South Africa, because of the high prevalence of HIV, has decided that all blood donations will be screened using a molecular-based assay that detect the nucleic acids of the HIV, HBV and HCV viruses in a multiplexed individual donation format in parallel with serological assays. In South Africa an additional 84 HIV infections, 232 HBV infections and 4 HCV infections in donations in 3 years have been detected using NAT (Table 2) and 22 HIV, 70 HBsAg and 87 anti-HCV infections that would not have been detected if using NAT alone. Interestingly, though, what can be seen from Table 3 is that although South Africa has the highest prevalence of HIV in the population, the implementation of a 100% voluntary donor base and >80% repeat donations decreases the prevalence of HIV in the donor population by 100-fold which is far lower than the other countries that have lower general population prevalence. This shows the importance of effective predonation counselling, collection of blood from safe donors and then testing as strategies to enhance the safety of blood donations.
Table 2. Number of reactive donations using different testing strategies in South Africa
Table 3. Prevalence of 1 11’s in various countries
|Central Africa Rep||13·5||15||18||2||12||5||1||80–100||0–20|
In conclusion, although screening is important in obtaining safe blood, it is equally important to collect blood from safe donors and so a concerted effort is required from governments and transfusion services to provide the financial resources required to implement a national blood system and to recruit and educate prospective voluntary blood donors and to work at getting these blood donors to become regular blood donors. At the same time, the testing laboratories should implement quality systems and use validated serology assays to test all blood donations in the country for transfusion transmissible infections in a standardized manner.