Introduction: The Role of Organ Transplantation in the Developing World

Africa is the most underdeveloped continent when it comes to transplantation options for patients with end-stage organ disease. Renal failure is a common condition, and for this reason exploring options for renal transplantation on the continent makes sense. However, starting a transplant program is a daunting task and despite previous meetings driven by the World Health Organization (WHO) in Africa (July 28–30, 2009, Abuja, Nigeria; December 5–6, 2008, Bamako, Mali) to discuss these issues, little development and progress has been made in Africa in this regard over the past few years. The issues in Africa are similar to many other parts of the developing world.

It is possible to look back on these meetings and try and explore why progress in the field of transplantation in the developing world is slow. One reason for this could be that these meetings did not provide enough practical tools to the clinicians who need to drive the process. Another reason could be that driving a process like transplantation requires a much larger group of people than those involved in these meetings.

Despite very limited transplant activity in Africa, successful transplant programs have been developed elsewhere in the developing world. In Pakistan a large living donor program has been established successfully with minimal cost to the patient. India’s living donor kidney program expanded rapidly over the past 10 years and now includes deceased donor and liver transplant from living donors. It is clear that there is a large spectrum of transplant activity in the developing world, ranging from places where there is almost no activity at all and where both living and deceased donation is still very limited, to other areas where transplant activity is rapidly expanding and growing.

Many groups are working on the improvement of transplantation access in the developing world: The Global Alliance for Transplantation (GAT) is a partnership between The Transplantation Society (TTS) and the WHO for the worldwide promotion of organ donation and transplantation activities consistent with the principles outlined in the Declaration of Istanbul, the World Health Assembly’s Resolution on Human Organ and Tissue Transplantation, and the Madrid Resolution on government accountability to achieve self-sufficiency in organ donation and transplantation. Many other members of the international transplantation community are trying to be of assistance to representatives of Africa and the developing world in identifying needs in the pursuit of transplantation, and in obtaining the commitment of governments for support in attaining this goal. The International Society of Nephrology and the Transplantation Society both sponsor programs in the developing world to establish ethical transplant practices.

Previous examples from Central and Eastern Europe and South America have demonstrated the effect of local leadership on the development of organ donation and transplantation programs. The South East Europe Initiative on Deceased Organ Donation (Macedonia, May 2011) and the Regional Health Development Centre in Organ Donation and Transplant Medicine in Croatia are two such examples of active and successful partnerships between clinicians, governments, and professional societies, which might in turn be applied in the African region. Several professional organizations are currently supporting clinicians to approach governments and to advocate for appropriate legislative frameworks and for the allocation of resources to transplantation, especially in settings where dialysis availability is rapidly outpacing the development of kidney transplantation.

Perspectives on Transplantation in the Developing World in Relationship to the World Health Organization Objectives

The last World Health Organization (WHO) consultation on cell, tissue, and organ transplantation in Africa occurred in Abuja, Nigeria in 2009. Nearly 10 years on, especially given shifting economic and demographic trends in the region, it is time to reappraise the situation with respect to organ donation and transplantation in Africa. Total health expenditure in sub-Saharan Africa is growing by 7% per annum. Healthcare expenditure is a crucial component of health status improvement in sub-Saharan African countries. Increasing healthcare expenditure is a significant step in achieving effective and safe treatment options for patients in the developing world. In many countries policymakers are establishing effective public-private partnerships in allocating healthcare expenditures. Therefore economic growth and corresponding increases in healthcare expenditures in the African region mean that we can confidently anticipate increased demand for organ transplantation within the region over the next few years. The WHO has a role to play in fostering these anticipated developments in accordance with the Guiding Principles on Human Cell, Tissue and Organ Transplantation.

The WHO is interested in every region of the globe and every level of development, not just in countries with well-established transplantation programs. The goal of the WHO is to achieve a common global attitude toward transplantation, via a multitude of partnerships with key bodies, including health authorities, scientific and professional societies, and experts. With respect to the development of the practice of deceased organ donation, the WHO endorses a four-step process: (1) adoption of the Critical Pathway for organ donation from deceased persons; (2) the drafting of a legal framework; (3) the development of a blueprint of a national system for organ donation from deceased donors; and (4) collaboration with government and the private sector for regional, subregional, and national implementation.

Ultimately it is medical professionals who are at the crossroads between donor, patient, and recipient. The practice of transplantation, and especially deceased donor organ transplantation, necessitates a level of trust in the transparency and professionalism of the health system. In addition to the responsibilities of health professionals, there is a need for public education to generate societal support for transplantation. Finally, there is an important role for governments in terms of commitment to allocation of resources, proper oversight, and the creation of an appropriate normative and legislative environment in which transplantation can operate. Engagement with health authorities is therefore appropriate from the earliest stages of program development. Furthermore, there is no legitimate transplantation activity that cannot be examined and monitored, and therefore registries for the surveillance of practices and outcomes are critical from the outset of the practice of organ transplantation.

In the context of developing health systems it will likely be necessary to engage the private sector in the development of transplantation services; however, such arrangements mandate complete transparency and specific and effective oversight from health authorities. Universal health coverage is a current major objective of WHO, with an emphasis on access, quality, and financial protection for all, based on financing systems designed to deliver cost effective services that do not expose the user to catastrophic costs. To achieve these goals with respect to the financing of organ transplantation, the engagement and commitment of governments will be essential.

As the practice of tissue, cell, and organ transplantation spreads around the world, there is a greater-than-ever need for global governance, upholding societal values of the protection of the donor, safety of the recipient, and self-sufficiency. An example of a project where vigilance and surveillance are actively encouraged and driven by the WHO is Project Notify. The WHO recognizes that there should be crosscutting principles surrounding medical products of human origin, based on global standards and consensus, and supported by global information standards and surveillance. Such tools will be of particular importance in the context of emerging health systems.

The WHO encourages a national strategy for organ donation and transplantation that: (1) promotes the integrated management of chronic kidney disease (CKD) from prevention to renal replacement therapies; (2) relies on existing guidance and multidisciplinary collaboration with a more advanced team, through long-term agreement between institutions and health authorities; (3) is mindful of the need for transparency of activities; (4) identifies organ donation after death as a long-term objective from the outset; (5) pioneers health system development and universal health coverage; and (6) uses donation and transplantation as an opportunity to create dynamics in health, and acts as an interface between the health system and the public.

The Need for Kidney Transplantation in the Developing World

Although we know that the availability of renal replacement therapy (RRT) is lower in low- and middle-income countries, it is realistic to estimate that there is a much greater need than in high-income countries as the true scale of the unmet need for treatment of end-stage kidney disease (ESKD) is unknown. Ideally, population-based studies, death registration data, and dialysis and transplant registries would enable quantitative estimation of the underlying burden of ESKD and its risk factors in the population. Yet although such data are largely unavailable, many have commented that the underlying burden of ESKD in Africa is likely to exceed that of high-income countries. First, because the underlying prevalence of risk factors associated with organ failure is known to be high, given increasing rates of noncommunicable diseases in the region, in particular diabetes and hypertension, combined with undiminished rates of infection-related nephropathies ( Figs. 38.1 and 38.2 ). Second, the nature of the primary causes of ESKD and the limited capacity for secondary prevention result in more rapid progression to organ failure than experienced in high income countries. Glomerular nephropathies and hypertension are the leading causes of treated ESKD in sub-Saharan Africa, accounting for between 18% to 50%, and 25% to 75% of all cases, respectively. Although diabetes currently accounts for between 3% and 24% of treated ESKD in sub-Saharan Africa (compared with 15%–60% in high-income countries), this proportion may increase given projections that the number of adults in Africa with diabetes will double by 2030.

Estimated prevalence (per million population [pmp], age-standardized) of hypertension and diabetes in African countries, compared with the United States and United Kingdom.

Source: WHO Global Health Observatory.

Estimated rate (per million population [pmp]) of mortality from nephritis and nephrosis in the population younger than 60 years in African countries, compared with the United States and United Kingdom.

Source: WHO Global Health Observatory, Global Burden of Disease Study.

Estimating the burden of ESKD in Africa is relevant because to effectively advocate for the allocation of resources to organ donation and transplantation, it is necessary to demonstrate that there is a need within the population for these services. “Need” may be defined as “the population’s ability to benefit from organ transplantation,” and has three aspects: (1) the underlying burden of organ failure and its risk factors, irrespective of current treatment availability or eligibility criteria; (2) the cost and efficacy of treatment (cost will constrain the number of people able to benefit from transplantation, and transplantation outcomes must be acceptable) and; (3) comparison to the existing provision of services.

The incidence of ESKD in Africa attributable to hypertension and diabetes might be estimated based on the cause-specific incidence of ESKD observed for the African American population. Based on an average adult prevalence of hypertension in the African region of 46%, and an incidence of ESKD with a primary diagnosis of hypertension in the US African American population of 0.7 per 1000 hypertensive adults, the incidence of ESKD due to hypertension in Africa potentially equals 330 cases per million adults aged >25 years. Similarly, based on an average adult prevalence of diabetes of 9% in Africa and an incidence of ESKD with a primary diagnosis of diabetes in the African American population of 2.1 per 1000 diabetic adults, the incidence of ESKD due to diabetes in Africa is estimated at 180 cases per million adults. HIV-related CKD is also likely to be responsible for a significant burden of ESKD in the African region: at least 400 cases per million population per year. If we extrapolate rates of progression to ESKD as reported for the African American population, then based on the high prevalence of hypertension, diabetes, and HIV in the African region, the annual incidence of ESKD potentially exceeds 900 cases per million adults owing to these three risk factors alone ( Fig. 38.3 ).

Estimated incidence of end-stage kidney disease in the sub-Saharan African adult (>25 years) population, by primary cause, based on cause-specific disease incidence extrapolated from the African American population.

For the subset of this population that might be considered medically suitable for transplantation, demand for transplantation will be tightly constrained by the availability of specialist physicians and surgeons, pathology facilities, capacity to achieve acceptable graft outcomes, cultural and religious attitudes toward organ donation, trust in the health system, and the extent to which patients are able to meet the costs of surgery and ongoing immunosuppression. Continuing demographic, epidemiologic, and economic shifts will have implications for the future incidence of organ failure in the African region and for the level of demand for high-level health care including transplantation; that is, the capacity of populations in Africa to benefit from transplantation will evolve in coming years. It is therefore timely to evaluate existing capability to deliver organ transplantation services in the African region, and to identify how local efforts, regional cooperation, and international partnerships can best address current constraints on the delivery of transplantation therapy.

Overview of Transplantation Activities in Africa

In Africa there are seven countries that are locally performing living-related donor transplantation: Ethiopia, Ghana, Kenya, Nigeria, Sudan, South Africa, and Tunisia. Programs vary between those that are well established with larger number of transplants (South Africa, Tunisia, Sudan) to small programs with a limited number of transplants in each center (Kenya, Ghana, Nigeria). South Africa has the highest rate of organ transplantation relative to its population (250 living-related donor kidney transplants in 2015), followed by Tunisia (122 living-related donor kidney transplants in 2015) and Sudan (165 living-related donor kidney transplants in 2015). An issue for Kenya and Nigeria is that there are many centers simultaneously trying to establish transplantation, with each center performing a limited number of transplants. In Nigeria there are six state and two private centers, where a total of 14 transplants were performed in 2015, and in Kenya there is one state and four private centers, which have performed a total of 60 transplants in 2015. This creates a problem of dispersal of expertise and facilities. None of the African countries except South Africa has yet commenced deceased donor transplantation. Transplant tourism and official arrangements in which governments send donor-recipient pairs abroad to undergo transplantation are relatively common. When patients travel for transplantation, destination countries include Tunisia (mostly patients from Cameroon), Pakistan and India (patients from Nigeria, Rwanda, Kenya, Zambia, and Malawi).

The majority of dialysis in African countries is conducted in state-run facilities, with the exception of Ethiopia and Tunisia. In Tunisia all transplantation activities are in state-run facilities, but the majority of dialysis takes place in private facilities. Private facilities contribute significantly to transplant activity in South Africa, Kenya, Nigeria, and Sudan, indicating a potentially significant role for public-private partnerships in the future development of transplantation in these countries. Cameroon, Malawi, Sudan, Tunisia, and Zambia have a central budget dedicated to dialysis; similarly, the costs of transplantation and posttransplant care are met by government or by private insurance in Cameroon, Malawi, Rwanda, Sudan, Tunisia, and Zambia. Elsewhere, patient costs are met by out-of-pocket payments. Organ donation and transplantation was said to be a priority in the further development of the health system in many African countries. Legislation pertaining to organ donation and transplantation is only in existence in South Africa, Tunisia, Sudan, Ghana, Nigeria, and Kenya.

Familiarity of doctors with the Declaration of Istanbul varies. Africa is a major potential destination for organ trafficking networks. The ongoing education of clinicians and health authorities is essential to prevent this practice from moving into Africa. In many other parts of the developing world organ trafficking is a major problem, especially in places where there are fairly good healthcare resources and minimal oversight.

Many existing successful partnership programs are in place trying to increase access to transplantation in Africa. These programs are being driven from a variety of European, North American, and South African centers.

Partnerships form a major part in developing transplantation services in Africa. Many US-based centers now reach out to Africa to perform global health projects. It is important that these partnerships result in education and training of local clinicians rather than simply going and performing a few transplants with surgeons from the developing world. To build up local practices and infrastructure, the programs need to include local surgeons and physicians in performing these procedures and looking after their own patients.

The importance of regional cooperation for transplantation in developing countries cannot be overstated. For example, in Tunisia 122 living-related transplants were performed in 2016. All of these were done in six centers in the state sector. This program certainly has the capacity to train other African clinicians in the future.

A similar situation exists in Sudan where 134 living donor transplants were performed in the state sector and 31 in the private sector in 2016. Current examples of regional cooperation for training include government sponsorship of nephrology trainees from Rwanda to travel to South Africa for specialist training. Cape Town has trained 20 nephrologists to date: Dr. Mweemba, the first nephrologist in the public systems in Zambia, was trained in South Africa and dialysis commenced in Zambia upon his return in 2009. Training for Zambian surgeons in South Africa is also planned. South Africa might also provide assistance and training for organ procurement to other African countries in the future. The African Development Bank are establishing an Institute of Nephrology and Urology, intended to train nephrologists and urologists in East Africa.

Many African patients still travel out of their country to receive a transplant. India is currently the most popular destination, mostly because of cost-effective packages and because renal physicians have relationships with hospitals in India. It might be useful to send donor-recipient pairs to countries within Africa for transplantation, rather than to India in the future. Currently Tunisia has cooperative agreements with Senegal and Cote d’Ivoire to transplant patients from these countries, and there are discussions regarding the feasibility of sending more donor-recipient pairs to South Africa for transplantation. The relative costs of immunosuppression in Africa versus India will need to be addressed before current practice shifts.

Pediatric transplantation is relatively rare in the developing world. Tunisia initiated pediatric transplantation early in the development of its living donor transplant program, constituting a good model for other countries in recognizing the importance of pediatric transplantation in the development of a transplantation program. Distance from pediatric kidney transplant centers may be a significant barrier in accessing care for patients and families, particularly because of the lower number of pediatric kidney transplant centers compared with the number of adult centers in the developing world.

Requirements for Living Versus Deceased Donor Transplantation

A topic of debate in the developing world is the relative resource requirements associated with living versus deceased donor transplantation and at what stage it is appropriate to contemplate deceased donor organ transplantation. Questions include: What is a sufficient level of dialysis availability? Should deceased donor transplantation be contemplated in parallel with the development of living donor transplantation? To what extent is it necessary to consolidate experience with living donor transplantation before commencing deceased donor transplantation? What are the minimum requirements in terms of ICU beds and trained personnel?

The experience of Tunisia illustrates the scale of the transition from provision of living donor transplantation to that of deceased donor transplantation. Despite a well-developed living donor transplantation program, which was established in 1986, deceased donor transplantation is not yet available. Barriers to the initiation of deceased donor transplantation in Tunisia were identified as an absence of legislation on brain death and the lack of infrastructure, personnel, and capacity for coordination required to support deceased donation. Whereas living donor transplantation might be successfully driven by a motivated individual and in a single institution, deceased donor transplantation requires dialysis programs, tissue typing and cross-matching facilities, an organ procurement program, an on-call surgical team, capacity to fund this infrastructure, and an appropriate legislative framework ( Fig. 38.4 ). Moreover, a significant level of regional/national organization is required: the historical experience of the US was that deceased donation gained momentum only when it was separated from the hospital and placed under an independent coordinating authority. There is also the need to contend with the public perception of deceased donation. It will be easier to commence deceased donation in the context of an established living donor program with acceptable and consistent recipient outcomes. Therefore in advocating for deceased donor transplantation, the requirements in terms of resources, infrastructure, track record, and capacity for coordination need to be realistically acknowledged.

Schematic diagram of the minimum requirements to perform deceased donor organ transplantation, and the interactions between these requirements.