In recent years, there has been a vast improvement in the organisation, management, clinical and technical aspects of transfusion services in sub-Saharan Africa,^9,10,11 although serious concerns remain with regard to the safety and adequacy of the blood supply.

According to the WHO recommended minimum of 10 units of donated blood per 1000 catchment population, an estimated 8–9 million units of blood are currently needed per year for transfusion in Africa.¹¹ In sub-Saharan Africa, 44% of maternal deaths are attributed to severe bleeding during pregnancy and childbirth.¹¹ Thus, the majority of blood products are used for treating pregnancy-related bleeding.¹¹ Another major group that receives blood transfusions are children; 50% of paediatric transfusions are for malaria-induced anaemia in children and other severe morbidities, notably anaemia from sickle-cell disease.¹²

Improving access to safe blood leads to improved healthcare. In Malawi, safer blood led to a 60% decrease in mortality amongst seriously ill children and a 50% decrease in mortality amongst pregnant women with severe blood loss.¹³ Many factors in sub-Saharan Africa contribute to the low availability of safe blood. Two major factors are low donation rates and a high prevalence of TTIs.^2,3,4,5,8,9

The blood donation rate in sub-Saharan Africa is generally low, with 4–5 per 1000 population^8,9 compared with 30 donations per 1000 in developed countries.² Thus, only 40% of targeted blood supply needs were realised by collection services in 2010.^2,9,14 According to WHO data,^8,9 blood transfusion from regular voluntary non-remunerated blood donors (VNRBDs) have the lowest risk of TTIs. However, VNRBDs represent less than 50% of whole blood donations in low-income countries compared with 76% – 100% in high-income countries.^8,9 The low VNRBD levels in some African countries may be a result not only of lack of organisation and financial resources, but also, to some extent, of socio-cultural barriers such as limited levels of education, religious and mystic beliefs and misconceptions about blood use.¹⁵

The high prevalence of TTIs, such as infection with HIV (5% amongst adults), hepatitis B virus (8%) and hepatitis C virus (10%),⁹ contributes to the poor supply, in terms of adequacy and safety.^2,3,4,9,10 Also important to note is that, of the estimated one million annual deaths resulting from malaria globally, 90% occur in sub-Saharan Africa.^7,9 This suggests a high carrier rate of malarial parasite in this region and hence in the pool of potential blood donors. According to the respondents of a 2010 survey of the status of blood safety in the WHO African Region, an estimated 7.5% of blood units were discarded to avoid the risks of TTIs.⁹ In high-income countries, donor screening and deferral procedures, as well as serologic testing and NAT, have helped to make blood a safer product, drastically reducing the risk of classical TTI agents such as HIV and hepatitis viruses.^3,4 However, whilst highly-sensitive techniques such NAT are available in high-income countries, screening and testing in low- and middle-income countries where the risk is highest, are limited to a combination of donor screening and/or deferral and serological procedures. High residual risks have been reported in African blood banks where NAT is not performed.⁴ NAT would allow identification of contaminated blood from donors who are in pre-serological phases of disease. However, this additional screening test is usually too expensive for the limited budgets of African blood services.

Another major difference between blood transfusion in low- and middle-income countries and high-income countries is that only 41.2% of all collections in Africa (1.4 million of 3.4 million) were transfused as components in 2010.⁹ Although there is increased use of components in sub-Saharan Africa, with the greatest need being for RBCs, it is expected that whole blood transfusions and red cell concentrates will continue to be the most requested units in the near future.^10,12

The aim of this review was to determine the suitability of pathogen reduction technology (PRT) for improving the safety of whole blood transfusions in sub-Saharan Africa, as well as for improving the adequacy of the blood supply available for transfusions. This technology could offer a way forward toward addressing the Millennium Development Goals in sub-Saharan Africa through helping to ensure an adequate and safe blood supply.

The situation described in the WHO 2010 survey⁹ was reinforced by the statements and presentations at the meetings in Brazzaville and Yaoundé^21,22,23 and is typified by the current state of affairs in Cameroon,²⁴ Ghana,⁵ Nigeria⁷ and the rest of sub-Saharan Africa.^5,15 Two key challenges in the region were highlighted: the overall inadequacy of the blood supply and the lack of safe blood for transfusions. These challenges are faced not only by women with pregnancy-related problems and children with paediatric malaria-induced anaemia,^8,9 but also by individuals with other severe, debilitating conditions such as sickle-cell disease. Sickle-cell disease is a genetic haemoglobinopathy, manifesting typically as life-threatening episodes or ‘crises’ (including a combination of moderate to severe pain, anaemia and other acute complications) related to venous occlusion.^25,26 With an estimated 200 000 infants born every year in Africa with sickle-cell disease and an estimated prevalence of 2%,²⁷ there are approximately 20 million people living with sickle-cell disease in sub-Saharan Africa. Because of the region’s growing population, this number will continue to increase. The effective management of sickle-cell disease in other regions suggests that 10% of a given population of sickle-cell disease patients require a life-saving transfusion each year to prevent strokes in children or to address acute complications in other groups.^27,28 Prognosis is poor across sub-Saharan Africa, with an 80% five-year mortality rate amongst children with sickle-cell disease, resulting from the lack of resources to ensure appropriate and safe management of life-threatening anaemia, amongst other issues.^27,29

Thus, added to the wider iatrogenic risks such as TTIs associated with transfusions,^5,6,7,8,9 the shortage of blood denies sickle-cell disease and many other patients in sub-Saharan Africa the adequate healthcare that is taken virtually for granted in Europe and North America.

There are a number of current technologies for the reduction of blood-borne pathogens.^19,20,21 These include systems for platelet concentrates and plasma, such as the Cerus Intercept system, which is based on psoralen; the Theraflex system, which is based on UVC irradiation; the Mirasol system, which is based on riboflavin and ultraviolet light; and the Cerus S-303 system, which is based on a DNA crosslinker. Presently, only two of the most prominent PRT platforms have the potential for whole blood treatment: the Mirasol PRT system for Whole Blood³⁰ and the Cerus S-303 system.³¹ A phase-III study has recently been completed for the Mirasol system for whole blood.^32,33 Thus, given the prominence of the whole blood transfusion format in sub-Saharan Africa, only the Mirasol PRT and Cerus S-303 systems were considered potentially suitable at the Brazzaville and Yaoundé stakeholder meetings.^18,19,20

Three key principles^18,19,20,34 would protect recipients from donor blood pathogens: improved donor selection/exclusion measures; improved and standardised methodology of testing; and reduction/removal of pathogens from the blood.

With regard to donor selection and/or exclusion, it should be pointed out that the WHO promotes VNRBD.³⁵ The WHO also sees the practice of family replacement donations, as exemplified in Cameroon,²⁴ as a risk to the blood supply because of the perceived potential of paid blood donation. However, there is some disagreement on the risk of this practice within the context of low-income countries, as some view the primary problem more as lack of available blood.³⁶ Family donation may not increase the risk to the blood supply in comparison to VNRBDs.³⁶ Furthermore, the establishment of VNRBDs as the only source of blood, as a policy, may not only increase the cost of a unit of blood by two- to five-fold and exacerbate the pre-existing blood shortage, but would hardly meet local blood supply needs.³⁶ It is also questionable whether hospital-based family replacement blood banks in Africa would ever be able to maintain adequate blood supplies to meet local needs. Some have reported that first-time VNRDs are no safer than family/replacement donors.³⁵

As for the testing of donated blood, the current practice in high-income countries is to employ the following layers of protection: donor screening, serology, NAT, leukoreduction, gamma irradiation and bacterial detection. Donors in high-income countries have a much lower prevalence of TTIs.^37,38 The outcome is that risk for TTIs in high-income countries is low for tested pathogens.^37,38 Typically, residual risk ranged from 1 in 300 000 units for hepatitis B virus in the United States, to 1 in 8 million units for HIV in Canada, to 1 in 11 million units for hepatitis C virus in Germany.^37,38 In contrast, in sub-Saharan Africa, residual risks were 4.3 in 1000 units for hepatitis B virus, 1 in 1000 units for HIV and 2.5 in 1000 units for hepatitis C virus from blood transfusion.³⁹ The WHO further reported inadequate quality assurance of donated blood, including unreliable vetting of the donor and serological testing of the donated blood, coupled with the practice of whole blood transfusion.¹³

Considering all of these factors, the current status of highly risky transfusion in sub-Saharan Africa requires a new paradigm approach. To start a combination of new technologies is needed that would be effective for whole blood transfusion – a significant format of transfusion in sub-Saharan Africa – and that could enhance the current testing solution for improved safety. Given the difficulty of recruiting sufficient donations, the proposed way forward should also have the potential to reduce supply wastage by rendering safe blood that would otherwise be rejected for testing positive. Amongst other attributes, the appropriate technology would need to exhibit: safety, effectiveness, clinical efficacy, physiological integrity of biological components, operational efficiency and competitive health economics. The various platforms encompassing PRT represent such a novel approach.^18,19,20 PRT platforms are already in use for platelets and plasma in many countries throughout Europe,^30,31 Asia and the Americas. With the emergence of platforms suitable for whole blood use,^{18,19,20,30,40} PRT now has the potential to offer an additional step in the standard blood safety value chain in sub-Saharan Africa. Moreover, the ability to inactivate pathogens in whole blood offers the flexibility of either using the blood as whole or, after inactivation, to subsequently separate the blood into components for storage.⁴⁰

We examined two PRT platforms in detail, the Mirasol PRT System for Whole Blood and the Cerus S-303 system. Both systems are based on disrupting the nucleic acid in the pathogen. The Mirasol system achieves this through electron transfer reactions, whereas the Cerus S-303 system does so through irreversible crosslinking of the DNA. We focused specifically on the toxicology of the systems to laboratory staff and patients and the potential usefulness of these two systems for whole blood transfusion.

The above limitations of toxicity (Cerus S-303 platform) and extra cost (both the Mirasol and Cerus S-303 platforms) notwithstanding, based on the underpinning pathogen nucleic binding chemistry, both PRT formats are potentially effective against a range of pathogens known and unknown, on white blood cells, as long as they contain nucleic acids. Moreover, by virtue of the underlying analytical sensitivity of the strategy, PRT has the potential of further closing the pathogen detection window period – when blood levels of specific pathogen markers are still below the detection limits of other methods (Figure 5).

This highlights the potential of PRT to markedly improve the safety of blood through a synergistic combination with the diagnostic window of testing. This conclusion came out of the seminars held with stakeholders, including clinicians, scientists and the WHO’s Regional Office for Africa, during the period of this study.^21,22,23

Given the high cost of establishing and running a blood componentisation programme, it might be beneficial for low- and middle-income countries to keep their focus on whole blood transfusions, increase blood donations and decrease the risk of exposure to pathogens in the blood supply, rather than on extensive componentisation. However, facilities permitting, the need for blood components might be met through apheresis, allowing blood banks to produce specific blood components based on the demand of the prescribing physician. That said, reduction of blood transfusion to their indispensable indications and appropriate use of blood components are critical to meet safe blood needs. This includes early diagnosis of diseases requiring blood transfusion, the use of surgical techniques and of medication aimed at limiting blood loss, as well as respect for national directives. In 2009, less than one out of 10 African countries had a proper policy in place for clinical use of blood.⁹ Inappropriate use of blood leads to blood shortages and increased risk of TTIs.

The provision of an adequate blood supply and safe transfusion of blood as recommended in the United Nations’ Millennium Development Goals remains a major challenge for sub-Saharan Africa. Current blood-borne pathogen testing arrangements, hampered by lack of adequate testing resources, result in TTIs at an estimated risk of 10% – 50% per transfusion. Moreover, because of poor blood donation rates, blood supplies at blood banks are low. This review supports the position that PRT may offer a solution for ensuring that the regionally dominant format of whole blood transfusion is rendered safer by removing TTIs. We suggest that a new paradigm toward combining PRT with standard quality testing would improve the safety of transfusion. The existing literature suggests that combining PRT with current routine blood screening methods (such as serology) would improve the safety of transfusions in sub-Saharan Africa. Following a detailed review of two of the leading PRT methods, the Terumo BCT Mirasol PRT Whole Blood system and the Cerus S-303 system, we suggest that manufacturers conduct a comprehensive toxicological evaluation of the agents used for PRT and publish their findings in the scientific literature. We also recommend that the safety and efficacy of PRT technology should be established in a randomised clinical trial conducted in sub-Saharan Africa, if the technology is adopted in the region.