Pediatr Transplantation 2014: 18: 668–674
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12333
Review Article
Challenges for paediatric transplantation in Africa Spearman CWN, McCulloch MI. (2014) Challenges for paediatric transplantation in Africa. Pediatr Transplant, 18: 668–674. DOI: 10.1111/petr.12333. Abstract: Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine. Long-term outcomes have significantly improved and the aim of management is no longer only long-term survival, but also focuses on quality of life especially in children. Transplantation in Africa faces a number of challenges including wide socioeconomic disparity, lack of legislation around brain death and organ donation in many countries, shortage of skilled medical personnel and facilities, infectious disease burden and insecure access to and monitoring of immunosuppression. Whilst there is a need for transplantation, the establishment and sustainability of transplant programmes require careful planning with national government and institutional support. Legislation regarding brain death diagnosis and organ retrieval/donation; appropriate training of the transplant team; and transparent and equitable criteria for organ allocation are important to establish before embarking on a transplant programme. Establishing sustainable, self-sufficient transplant programmes in Africa with equal access to all citizens is an important step towards curtailing transplant tourism and organ trafficking and has a further beneficial effect in raising the level of medical and surgical care in these countries.
Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver, and intestine.
Abbreviations: AIDS, acquired immunodeficiency syndrome; AFPNA, African Paediatric Nephrology Association; AFRAN, African Association of Nephrology; CMV, cytomegalovirus; EBV, epstein-barr virus; ESPGHAN, European Society of Hepatology, Gastroenterology and Nutrition; GAT, The Global Alliance for Transplantation; HIV, human immunodeficiency virus; IPNA, International Paediatric Nephrology Association; IPTA, International Paediatric Transplantation Association; ISN, International Society of Nephrology; ISPD, International Society of Peritoneal Dialysis; TTS, The Transplantation Society; WHO, World Health Organization.
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C. W. N. Spearman1,2,3 and M. I. McCulloch1,4 1
Red Cross Children’s Hospital, University of Cape Town Medical School, Cape Town, South Africa, 2 Groote Schuur Hospital, University of Cape Town Medical School, Cape Town, South Africa, 3 Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa, 4 Department of Paediatrics, University of Cape Town Medical School, Cape Town, South Africa
Key words: paediatric transplantation – Africa – challenges C. W. N. Spearman, Division of Hepatology, Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa Tel.: +27 21 4066394 Fax: +27 21 4486815 E-mail: [email protected] Accepted for publication 12 July 2014
Long-term outcomes have significantly improved with advances in surgical techniques, anaesthetic management, pre- and post-operative care and improvements in immunosuppression. The aim of the management is no longer only long-term survival, but also focuses on quality of life especially in children. According to data from WHO: Global Observatory on Donation and Transplantation, approximately 112 600 solid organs were transplanted in 2011, a 5.1% increase over 2010 (1). However, the majority of these transplants occurred in North America, United Kingdom, Europe, Australia, and increasingly in South America. In Africa, the only documented transplant activity is in South Africa, Egypt, Morocco,
Challenges for paediatric transplantation
Algeria, Libya, Tunisia, Kenya, Nigeria, Ghana, and Sudan, and this is predominantly living related (2, 3). Programmes vary from well-established programmes with a relatively large number of transplants (South Africa, Egypt, Tunisia, and Sudan) to very small programmes with a small number of transplants being performed in each centre (Kenya, Ghana, and Nigeria). Tunisia has the highest rate of organ transplantation relative to its population (122 living-related donor kidney transplants in 2012), followed by Sudan (165 living-related kidney transplants) (2, 3). Paediatric kidney transplantation is mainly limited to Egypt, Tunisia, Morocco, and South Africa with isolated paediatric renal transplants in Kenya and Nigeria. Although Egypt performs living-related kidney and liver transplants in children, South Africa is the only sub-Saharan African country where both living-related and deceased donor kidney and liver transplantation are performed in children. In Kenya and Nigeria, there are many centres simultaneously trying to establish transplantation, with each centre performing a limited number of transplants. Nigeria has six state and two private centres, which performed 14 renal transplants in 2012, and Kenya has four private centres and one state centre, which performed 60 renal transplants in 2012. This lack of centralization creates a problem of dispersal of medical/ surgical expertise and allocation of health resources (2, 3), but also provides an opportunity for public/private partnerships to promote development of transplant programmes. Currently, there is no formal paediatric heart or lung transplant programme outside of South Africa. The need for paediatric transplant programmes is often driven by parents of sick children seeking transplantation from centres abroad. Private and public funds are raised to fund the costs of the initial surgery. However, on return home, there is often no organized followup or secure access to long-term immunosuppression or monitoring thereof, and children demise from lack of monitoring, poor adherence, rejection, and complications of immunosuppression. Teenagers in particular with non-compliance issues may have little support especially at the time of transition to adult services (4). In African countries with better health resources (Egypt, South Africa, Nigeria, Kenya, Ghana, Sudan, and Tunisia), state transplant programmes have been established, but are still faced with challenges of manpower training and equitable allocation of health resources (2, 3, 5).
Frequently, private transplant centres have been developed to which only the wealthy have access. These private centres often act as referral centres for neighbouring countries which do not have transplant programmes and this increases the potential risk of transplant tourism. Developing national transplant services or formal government referral systems to neighbouring countries for living-related transplantation as exists between Tunisia and Senegal/Cote d’Ivoire and which is accessible to all citizens is important as the need exists and will help reduce the need for transplant tourism (2, 6). Establishment of successful transplant programmes requires a coordinated infrastructure involving a number of key role players
• • • • • • • • • • • • • •
Transplant surgeons/physicians/coordinators Anaesthetists/intensivists/theatre staff Trained nursing staff Tissue immunologists Radiologists Microbiologists/virologists/pathologists/biochemists and haematologists Blood bank services Social workers/psychologists/psychiatrists Neurodevelopmental assessments Occupational therapists/physiotherapists Pharmacists Dieticians 24-h laboratory and radiological services Institutional ethics committee
But, importantly, there needs to be support from the country’s National Department of Health and local hospital administrators to ensure long-term sustainable programmes. The positive impact on the development of organ donation and transplantation programmes of cooperative partnerships between clinicians and national governments supported by the TTS has been demonstrated in Central and Eastern Europe (7–9). Transplant programmes in developing countries including Africa are often initiated by enthusiastic surgeons supported by visiting transplant surgeons from established overseas transplant centres. It is well documented that visiting transplant surgeons together with local surgeons will undertake to perform a series of kidney transplants within a centre. Although the surgery is usually successful, problems often occur with long-term follow-up and inadequate training of physicians involved in the long-term management of the transplant recipient including availability of 669
Spearman and McCulloch
immunosuppressive drugs. Local situations including traditions, social and religious beliefs, as well as local prevalence of infections such as tuberculosis and malaria may not be understood. Whilst a mentoring system involving twinning with either an established paediatric or adult transplant programme is highly beneficial, the aim should always be to make a transplant centre within a developing country self-sufficient. There is a growing trend to include global health in the training of health professionals which will assist in the better understanding of local conditions as well as continue developing “twinning” links (10). A transplant team needs to be trained in all aspects of transplantation Pretransplant care and assessment
There needs to be established protocols addressing inclusion and exclusion criteria appropriate to the resource constraints of a country. It is important to address the expectations of both the family and referring doctor regarding both pre-transplant and lifelong post-transplant care, the need for lifelong immunosuppression, and the reality of death on the waiting list. Nutritional support whilst awaiting transplantation is crucial. The responsibility of the primary medical caregiver does not end on referral to a transplant centre, but should continue with follow-up posttransplantation. Psychosocial and neurodevelopmental assessments pretransplant and the appropriateness of transplantation are important issues to address, particularly in resource-limited countries. Intra-operative and immediate post-operative management
Surgical, anaesthetic, intensive care, and nursing protocols need to be established, and these need to be discussed with the appropriate stakeholders. Paediatric patients may often be managed in adult units, and thus, there may need to be members of both teams present to facilitate management. Post-transplant follow-up and long-term care
These involve clinical and biochemical follow-up of graft function and careful drug-level monitoring. Long-term care needs to address adherence, complications of immunosuppression, and importantly, transition of adolescents to adult services. Sustainability
Transplant programmes are frequently initiated by enthusiastic well-trained surgeons, but in 670
order for a programme to be successful, there needs to be a multidisciplinary team approach to the care of a transplant recipient with national government and local centre administrative support. Transplantation, particularly long-term care, is expensive, and the responsibility of these costs needs to be discussed at national level so that all citizens have potential access to transplantation. There needs to be on-going training of medical, paramedical, and nursing staff as well as adequate funding of individuals within a transplant team and transplant centres. Transplant centres together with government support need to commit to lifelong care of transplant recipients and secure access to lifelong immunosuppression. Special problems facing paediatric transplant programmes in Africa
There are often wide socio-economic disparities within Africa including South Africa with differences in the level of facilities and medical care available in rural and urban areas as well as between the state and private sector. Transplant assessment
Children are frequently referred late for transplant assessment as transplantation is still seen as a last resort. These children are frequently malnourished with severe failure to thrive and have multi-organ involvement. Socio-economic factors play a crucial role in the potential success of transplantation. Parents are frequently unemployed, may be caring for many other children or other family dependants and rely on child support grants. Children and families living in rural areas often have no electricity, inadequate sanitation and water supply. They may be reliant on pit toilets, have no running water, and are dependent on collecting water from rivers. Even those living in urban areas may live in informal settlements and rely on shared amenities such as communal taps and toilets. Not infrequently, these families may not have enough food for all meals which also affects how the immunosuppressive drugs are given, that is, drugs should be taken with meals. The burden of infectious disease such as tuberculosis (TB), viral infections (hepatitis B and C, HIV), malaria, and parasitic infections is high in many African countries and may preclude a child from transplantation. This also increases the potential risk of transmission of infections from the donor, including HIV, hepatitis B and C, schistosomiasis, strongyloides, and Chaga’s disease. This is further exacerbated
Challenges for paediatric transplantation
if access to appropriate and accurate infectious screening of the recipient and donor is not possible. Hepatitis B is endemic in Africa and the presence of occult hepatitis B in the donor still carries the risk of transmission and development of de novo hepatitis B, especially in liver transplant recipients (11, 12). In TB endemic regions, disseminated and extrapulmonary cases are being reported in transplant patients (13, 14), and Isoniazid prophylaxis should be considered. TB drugs such as rifampicin, which are metabolized by the cytochrome p450 system, significantly lower calcineurin inhibitor levels, and thus, higher doses are required with accompanying increased costs and increased risk of graft rejection if the dosage of calcineurin inhibitors is not appropriately increased. Post-transplant infections are important causes of morbidity and mortality post-transplant (15). CMV and EBV infection is endemic in Africa (16, 17) and children are infected with EBV early in life, usually seroconverting by age of three yr (18). These infections can trigger rejection of the transplanted organ and increase the risk of post-transplant lymphoproliferative disease. There needs to be on-going intensive medical care and nutritional support of children awaiting transplantation. Access to medical care is frequently a problem. Children and their families often live in rural areas, and it is important to establish the distance to the local clinic, district hospital, and tertiary centre and whether they have appropriate transport. Hospital funded transport for follow-up visits may not be available, and exorbitant taxi costs may be incurred as both carer and patient are charged. One needs to know the level of medical care available at their nearest health facility – can medical queries be correctly answered and can graft function and immunosuppressive drug levels be monitored; is there access to immunosuppression; and can they be admitted for medical management of complications. Many potential transplant recipients from rural areas within developing countries may live 1000 km from the nearest transplant centre, making it essential to assess whether the child and the family can temporarily relocate (often for many months at a time) to the transplant centre whilst awaiting transplant and until they are stable enough to return home. Post-transplant care
There is frequently a single transplant centre for the whole country. The transplant recipient is a
patient for life, requiring monitoring of graft function and management of long-term complications. Patients frequently return home where there is a lack of a 24-h medical facility. There is usually no dedicated post-transplant clinic or even a dedicated medical caregiver. Communication with the transplant centre on the recipient’s return home is frequently erratic. These problems need to be addressed pre-transplant so that recipients can be selected appropriately and referring medical caregivers informed of their responsibilities in shared medical care both pre- and post-transplantation. The transplant centres need to identify contact medical personal in referring hospitals and establish modes of communication either telephonically or using newer modalities such as email or texting (SMS) to ensure successful long-term follow-up of transplant recipients. Adolescents
“Normal” teenage behaviour and issues of noncompliance play a significant role in resource poor regions as these young people may often only have one “chance” at an organ transplant due to the shortage of organs and these patients not being seen as a “good” investment for retransplantation compared with more mature adult patients. Transition programmes from paediatric to adult services may also not exist (4). Donors
In many countries in Africa, the access to braindead heartbeating donors is limited for a number of reasons including religious, cultural, lack of legal recognition of brain death, but also importantly lack of support for transplantation from medical staff and hospital administrations. Promulgation of legislation regarding organ donation and transplantation may be necessary before a transplant programme can be developed. The majority of African countries rely on living-related donation, and there needs to be detailed protocols in place to ensure adequate screening of and long-term follow-up of livingrelated donors. In addition, many proposed donors may be single parents who are the solebread winners and thus are financially dependent on being able to perform their jobs and not having prolonged periods of sick leave. There is often no organized network for organ sharing, making urgent transplantation and re-transplantation difficult or even impossible. Frequently, private and state programmes compete for donors and the poor are further disadvantaged. 671
Spearman and McCulloch Transplant tourism and organ trafficking
In countries where there is wide socio-economic disparity, limited access to transplantation and lack of legal legislation on organ donation, there is always the risk of organ trafficking and transplant tourism. Fortunately, most countries have now endorsed the Istanbul Declaration on organ trafficking and transplant tourism (19–21). In countries with no established transplant centres, parents either independently or as part of an official government arrangement travel abroad as donor–recipient pairs for living-related transplantation. Common destinations include India, Pakistan, Tunisia, and South Africa. Unfortunately, there is often inadequate oversight with regard to establishing whether the donor and recipient are related or known to each other, and to the safety of the recipient and donor. The recipients and their donors may return to their home countries very soon posttransplantation often with complications and in some cases with very little medical information about what happened peri-operatively and without a protocol for post- transplant care or ensured access to immunosuppression. Ethical considerations
In order for there to be equitable access to transplantation, there needs to be state-funded programmes. However, in African countries with limited health resources, the governments need to exercise responsible stewardship and direct their limited health budgets to the eradication of malaria, HIV/AIDS, tuberculosis, gastroenteritis, and malnutrition and ensure appropriate prophylactic immunization of the population as well as community health education programmes. It is therefore not appropriate that every country in Africa has its own transplant programme, but it is important to identify and support countries that have the capacity and could act as official referral centres for living-related transplantation and as centres to train medical staff in the post-transplant care of transplant recipients. In July 2013, GAT, a partnership between TTS and the WHO, for the worldwide promotion of organ donation and transplantation activities held a symposium in Durban, South Africa, to assess the need for and obstacles to transplantation and obtaining government support in sub-Saharan Africa and to develop/promote mentoring schemes with well-established transplant programmes. Eleven countries based on their need and ability to develop a transplant programme were invited to participate (Cameroon, Ethiopia, Ghana, Kenya, Malawi, 672
Nigeria, Rwanda, Senegal, Sudan, Tunisia, and Zambia) (2, 3). A major obstacle to sustainable transplantation is the cost of long-term immunosuppression. National governments together with the International Transplant Community should consider lobbying pharmaceutical companies collectively for Africa for access to affordable immunosuppressive drugs including low-cost generic drugs in the same way as anti-retroviral therapy was provided for Africa. The role of scientific organizations
There has been an increased awareness by scientific and professional societies, especially in developed countries of their responsibility to assist in ongoing education and training in developing countries. In Africa, some specific examples have included the ESPGHAN which has been running twice yearly one-wk workshops and have twinned with pharmaceutical sponsors to fly participants from various parts of Africa for training in these fields. This increases the basic knowledge and sets the foundation for eventual transplantation. Similarly, renal societies such as the IPNA and their adult counterpart the ISN have provided 1– 2-yr fellowship training programmes to establish knowledge in renal disease including the assessment and follow-up of renal transplant patients. The ideology has been to train African fellows in centres of excellence in Africa which has not only improved understanding of local disease pathologies, but also limited the number of fellows who travel to train in developed countries, never to return to Africa. More recently, several organizations have worked together as an initiative called Saving Young Lives (including IPNA/ISN/ISPD and Sustainable Kidney Care Foundation) to provide one-wk training courses in nephrology, specifically hands-on approaches to initiating acute dialysis with pharmaceutical companies providing supplies with a view to later developing chronic dialysis. Finally, following the successful establishment of Adult Sister Centre Programmes such as those offered by ISN and TTS in terms of manpower and specifically surgical training, whereby a centre from a developing country and developed country twin for support – including visits over a 1–3-yr period depending on level of exchange (Category A, B, and C from basic support [C] to highest level of support [A]). Paediatric organizations such as IPNA and IPTA have implemented similar programmes (personal communication
Challenges for paediatric transplantation
MI McCulloch – currently on Council of IPNA as Sister Centre Chair and IPTA Council). Membership reduction for developed countries has also been implemented by many organizations, and in some cases, this has been done in conjunction with local organizations to allow these to be established, for example, currently 50% IPNA registration is paid to the International society and 50% goes to the local AFPNA. Use of modern technology such as online training and webinars further enhances these scientific organizations’ support. Recommendations for establishing paediatric transplant programmes in Africa
Established transplant programmes in Africa (South Africa and Egypt) have usually first established a renal dialysis programme, ensured that the required complex infrastructure is in place and then started with an adult renal transplant programme before embarking on paediatric renal transplant programmes. The infrastructure required for deceased organ donation is significant: legal and cultural recognition of brain death, independent determination of the neurological criteria for brain death in an intensive care unit in a patient on mechanical ventilation, tissue typing and cross-matching facilities, an organ procurement programme and an on-call surgical team (3). Renal transplantation programmes should start with livingrelated programmes and once the appropriate infrastructure is in place, consider deceased donation. Once a successful renal transplant programme is in place, a country can then assess the need to establish their own liver, heart, lung, pancreas, and intestinal transplant programmes. Establishment of these more complex solid organ transplant programmes will not be appropriate for most African countries, but the establishment of a successful renal transplant programme will enable the transplant medical fraternity to follow up other solid organ transplant recipients as part of shared care. To achieve an equitable balance, governments may need to institute funding streams for various levels of health care: primary, secondary, and tertiary health care with resultant rationing at each level, for example, limited number of renal dialysis slots according to budget. This also requires the government sector to centralize tertiary services to allow an adequate volume of high-cost and complex procedures such as transplantation to be performed with adequate skill and expertise in only three or four
centres around a country initially depending on the population and geographic area. It is important to establish transplant donor and recipient registries to ensure transparency by documenting transplant activity in the private and state sector, waiting lists, short- and longterm outcomes as well as donor morbidity and mortality. This registry data also provide an objective basis for advocacy for transplantation. The establishment of organ donor foundations is important to educate and increase public awareness about the need and benefits of organ donation. The International Transplant Community should play an ongoing active role in the education and training of the transplant community in Africa and provide a forum at international meetings where African transplant programmes can present their outcomes. Conclusion
Successful transplant programmes have been established in Africa (2, 12, 22–28), despite major obstacles. The establishment of transplant programmes requires careful planning with national government support, and a multidisciplinary team approach with mentoring of staff is important. It is often beneficial to share resources and skills between adult and paediatric programmes as well as regional networking (22, 23, 28, 29). Twinning with established overseas programmes helps to improve the skills base, but the ultimate aim should be to enable local transplant programmes to be self-sufficient in all aspects of medical and surgical care of the transplant recipient. Private–public partnerships enabling sharing of skills base and resources and equitable sharing of donors should be encouraged. Secure access to lifelong medical care and subsidized immunosuppression (not just short term for the first 2–3 yr), so that all citizens within a country have potential access to transplantation, is crucial before embarking on a transplant programme. Although expensive and labourintensive, successful transplant programmes have the added benefit of raising the general level of medical and surgical care in a transplant centre, which not only benefits other patients, but also helps to retain highly skilled medical personnel. References 1. WHO. Global Observatory on Donation and Transplantation. Available at: www.transplant-observatory.org (accessed 2 May 2014).
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Spearman and McCulloch 2. REPORT OF THE GLOBAL ALLIANCE FOR TRANSPLANTATION WORKSHOP. Awaiting publication personal communication ELMI MULLER. 29–30 July 2013. Durban, KwaZulu-Natal, South Africa. 3. MULLER E, WHITE S, DELMONICO F. Regional perspective: Developing organ transplantation in sub-Saharan Africa. Transplantation 2014: 97: 975–976. 4. HARDEN PN, WALSH G, BANDLER N, et al. Bridging the gap: An integrated paediatric to adult clinical service for young adults with kidney failure. BMJ 2012: 344: e3718. 5. QUAK SH. Liver transplantation in the developing world. Curr Opin Organ Transplant 2009: 14: 540–543. 6. AKOH JA. Renal transplantation in developing countries. Saudi J Kidney Dis Transpl 2011: 22: 637–650. 7. GOPCEVIC A, VUCIC M, LOVRENCIC-HUZJAN A, et al. Increased donor rate at Sestre milosrdnice University Hospital. Acta Clin Croat 2009: 48: 319–324. 8. SPASOVSKI G, BUSIC M, PIPERO P, et al. Current status of transplantation and organ donation in the Balkans–could it be improved through the South-eastern Europe Health Network (SEEHN) initiative? Nephrol Dial Transplant 2012: 27: 1319– 1323. 9. ZIVCIC-COSIC S, BUSIC M, ZUPAN Z, et al. Development of the Croatian model of organ donation and transplantation. Croat Med J 2013: 54: 65–70. 10. MOLYNEUX E, O’HARE B. The value of including global health in the training of health professionals. Arch Dis Child 2013: 98: 840–842. 11. LEE KH, CHUN TW, LIM SG, et al. Risk for de novo hepatitis B from antibody to hepatitis B core antigen-positive donors in liver transplantation in Singapore. Liver Transplant 2001: 7: 469–470. 12. BOTHA JF, SPEARMAN CW, MILLAR AJ, et al. Ten years of liver transplantation at Groote Schuur Hospital. S Afr Med J 2000: 90: 880–883. 13. BOUBAKER K, GARGAH T, ABDERRAHIM E, BEN ABDALLAH T, KHEDER A. Mycobacterium tuberculosis infection following kidney transplantation. Biomed Res Int 2013: 2013: 347103. 14. HSU MS, WANG JL, KO WJ, et al. Clinical features and outcome of tuberculosis in solid organ transplant recipients. Am J Med Sci 2007: 334: 106–110. 15. ULLAH K, REZA S, AHMED P, et al. Posttransplant infections: Single centre experience from the developing world. Int J Infect Dis 2008: 12: 203–214.
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16. KRECH U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ 1973: 49: 103–106. 17. ADJEI AA, ARMAH HB, GBAGBO F, BOAMAH I, ADU-GYAMFI C, ASARE I. Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa. BMC Infect Dis 2008: 8: 111. 18. BIGGAR RJ, HENLE W, FLEISHER G, BOCKER J, LENNETTE ET, HENLE G. Primary Epstein-Barr virus infections in African infants. I. Decline of maternal antibodies and time of infection. Int J Cancer 1978: 22: 239–243. 19. Participants in the International Summit of Transplant Tourism and Organ Trafficking, Convened by The Transplantation Society and International society of Nephrology. The declaration of Istanbul on organ trafficking and transplant tourism. Clin J Am Soc Nephrol 2008; 10: 1227–1231 20. STEERING COMMITTEE OF THE ISTANBUL SUMMIT. Organ trafficking and transplant tourism and commercialism: The Declaration of Istanbul. Lancet 2008: 372: 5–6. 21. AKOH JA. Key issues in transplant tourism. World J Transplant 2012: 2: 9–18. 22. SPEARMAN CWN, MCCULLOCH M, MILLAR AKW, et al. Liver transplantation at Red Cross War Memorial Children’s Hospital. S Afr Med J 2006: 96: 960–963. 23. MCCULLOCH MI, GAJJAR P, SPEARMAN CWN, et al. Overview of a paediatric renal transplant programme. S Afr Med J 2006: 96: 955–959. 24. MILLAR AJ, HAMZA AF. Liver transplantation in an African setting. Semin Pediatr Surg 2012: 21: 164–171. 25. KHALAF H, EL-METENI M, EL-SEFI T, et al. Evolution of living donor liver transplantation in Egypt. Saudi Med J 2005: 26: 1394–1397. 26. HADDIYA I, RADOUI A, BENAMAR L, et al. Ten years of renal transplantation in a Moroccan hospital: Results and constraints. Transplant Proc 2012: 44: 2976–2981. 27. BARDI R, CHERIF M, GOUCHA R, et al. Kidney transplantation: Charles Nicolle Hospital experience. Transplant Proc 2009: 41: 651–653. 28. LOVELAND JA, GOVENDER T, BOTHA J, BRITZ R. Paediatric liver transplantation in Johannesburg: Initial 29 cases and prospects for the future. S Afr Med J 2012: 7: 233–236. 29. SPASOVSKI G, DOHCEV S, STANKOV O, et al. The improvement in kidney transplant program in R. Macedonia – what are the clues? Prilozi 2013: 34: 9–13.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12333
Review Article
Challenges for paediatric transplantation in Africa Spearman CWN, McCulloch MI. (2014) Challenges for paediatric transplantation in Africa. Pediatr Transplant, 18: 668–674. DOI: 10.1111/petr.12333. Abstract: Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine. Long-term outcomes have significantly improved and the aim of management is no longer only long-term survival, but also focuses on quality of life especially in children. Transplantation in Africa faces a number of challenges including wide socioeconomic disparity, lack of legislation around brain death and organ donation in many countries, shortage of skilled medical personnel and facilities, infectious disease burden and insecure access to and monitoring of immunosuppression. Whilst there is a need for transplantation, the establishment and sustainability of transplant programmes require careful planning with national government and institutional support. Legislation regarding brain death diagnosis and organ retrieval/donation; appropriate training of the transplant team; and transparent and equitable criteria for organ allocation are important to establish before embarking on a transplant programme. Establishing sustainable, self-sufficient transplant programmes in Africa with equal access to all citizens is an important step towards curtailing transplant tourism and organ trafficking and has a further beneficial effect in raising the level of medical and surgical care in these countries.
Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver, and intestine.
Abbreviations: AIDS, acquired immunodeficiency syndrome; AFPNA, African Paediatric Nephrology Association; AFRAN, African Association of Nephrology; CMV, cytomegalovirus; EBV, epstein-barr virus; ESPGHAN, European Society of Hepatology, Gastroenterology and Nutrition; GAT, The Global Alliance for Transplantation; HIV, human immunodeficiency virus; IPNA, International Paediatric Nephrology Association; IPTA, International Paediatric Transplantation Association; ISN, International Society of Nephrology; ISPD, International Society of Peritoneal Dialysis; TTS, The Transplantation Society; WHO, World Health Organization.
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C. W. N. Spearman1,2,3 and M. I. McCulloch1,4 1
Red Cross Children’s Hospital, University of Cape Town Medical School, Cape Town, South Africa, 2 Groote Schuur Hospital, University of Cape Town Medical School, Cape Town, South Africa, 3 Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa, 4 Department of Paediatrics, University of Cape Town Medical School, Cape Town, South Africa
Key words: paediatric transplantation – Africa – challenges C. W. N. Spearman, Division of Hepatology, Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa Tel.: +27 21 4066394 Fax: +27 21 4486815 E-mail: [email protected] Accepted for publication 12 July 2014
Long-term outcomes have significantly improved with advances in surgical techniques, anaesthetic management, pre- and post-operative care and improvements in immunosuppression. The aim of the management is no longer only long-term survival, but also focuses on quality of life especially in children. According to data from WHO: Global Observatory on Donation and Transplantation, approximately 112 600 solid organs were transplanted in 2011, a 5.1% increase over 2010 (1). However, the majority of these transplants occurred in North America, United Kingdom, Europe, Australia, and increasingly in South America. In Africa, the only documented transplant activity is in South Africa, Egypt, Morocco,
Challenges for paediatric transplantation
Algeria, Libya, Tunisia, Kenya, Nigeria, Ghana, and Sudan, and this is predominantly living related (2, 3). Programmes vary from well-established programmes with a relatively large number of transplants (South Africa, Egypt, Tunisia, and Sudan) to very small programmes with a small number of transplants being performed in each centre (Kenya, Ghana, and Nigeria). Tunisia has the highest rate of organ transplantation relative to its population (122 living-related donor kidney transplants in 2012), followed by Sudan (165 living-related kidney transplants) (2, 3). Paediatric kidney transplantation is mainly limited to Egypt, Tunisia, Morocco, and South Africa with isolated paediatric renal transplants in Kenya and Nigeria. Although Egypt performs living-related kidney and liver transplants in children, South Africa is the only sub-Saharan African country where both living-related and deceased donor kidney and liver transplantation are performed in children. In Kenya and Nigeria, there are many centres simultaneously trying to establish transplantation, with each centre performing a limited number of transplants. Nigeria has six state and two private centres, which performed 14 renal transplants in 2012, and Kenya has four private centres and one state centre, which performed 60 renal transplants in 2012. This lack of centralization creates a problem of dispersal of medical/ surgical expertise and allocation of health resources (2, 3), but also provides an opportunity for public/private partnerships to promote development of transplant programmes. Currently, there is no formal paediatric heart or lung transplant programme outside of South Africa. The need for paediatric transplant programmes is often driven by parents of sick children seeking transplantation from centres abroad. Private and public funds are raised to fund the costs of the initial surgery. However, on return home, there is often no organized followup or secure access to long-term immunosuppression or monitoring thereof, and children demise from lack of monitoring, poor adherence, rejection, and complications of immunosuppression. Teenagers in particular with non-compliance issues may have little support especially at the time of transition to adult services (4). In African countries with better health resources (Egypt, South Africa, Nigeria, Kenya, Ghana, Sudan, and Tunisia), state transplant programmes have been established, but are still faced with challenges of manpower training and equitable allocation of health resources (2, 3, 5).
Frequently, private transplant centres have been developed to which only the wealthy have access. These private centres often act as referral centres for neighbouring countries which do not have transplant programmes and this increases the potential risk of transplant tourism. Developing national transplant services or formal government referral systems to neighbouring countries for living-related transplantation as exists between Tunisia and Senegal/Cote d’Ivoire and which is accessible to all citizens is important as the need exists and will help reduce the need for transplant tourism (2, 6). Establishment of successful transplant programmes requires a coordinated infrastructure involving a number of key role players
• • • • • • • • • • • • • •
Transplant surgeons/physicians/coordinators Anaesthetists/intensivists/theatre staff Trained nursing staff Tissue immunologists Radiologists Microbiologists/virologists/pathologists/biochemists and haematologists Blood bank services Social workers/psychologists/psychiatrists Neurodevelopmental assessments Occupational therapists/physiotherapists Pharmacists Dieticians 24-h laboratory and radiological services Institutional ethics committee
But, importantly, there needs to be support from the country’s National Department of Health and local hospital administrators to ensure long-term sustainable programmes. The positive impact on the development of organ donation and transplantation programmes of cooperative partnerships between clinicians and national governments supported by the TTS has been demonstrated in Central and Eastern Europe (7–9). Transplant programmes in developing countries including Africa are often initiated by enthusiastic surgeons supported by visiting transplant surgeons from established overseas transplant centres. It is well documented that visiting transplant surgeons together with local surgeons will undertake to perform a series of kidney transplants within a centre. Although the surgery is usually successful, problems often occur with long-term follow-up and inadequate training of physicians involved in the long-term management of the transplant recipient including availability of 669
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immunosuppressive drugs. Local situations including traditions, social and religious beliefs, as well as local prevalence of infections such as tuberculosis and malaria may not be understood. Whilst a mentoring system involving twinning with either an established paediatric or adult transplant programme is highly beneficial, the aim should always be to make a transplant centre within a developing country self-sufficient. There is a growing trend to include global health in the training of health professionals which will assist in the better understanding of local conditions as well as continue developing “twinning” links (10). A transplant team needs to be trained in all aspects of transplantation Pretransplant care and assessment
There needs to be established protocols addressing inclusion and exclusion criteria appropriate to the resource constraints of a country. It is important to address the expectations of both the family and referring doctor regarding both pre-transplant and lifelong post-transplant care, the need for lifelong immunosuppression, and the reality of death on the waiting list. Nutritional support whilst awaiting transplantation is crucial. The responsibility of the primary medical caregiver does not end on referral to a transplant centre, but should continue with follow-up posttransplantation. Psychosocial and neurodevelopmental assessments pretransplant and the appropriateness of transplantation are important issues to address, particularly in resource-limited countries. Intra-operative and immediate post-operative management
Surgical, anaesthetic, intensive care, and nursing protocols need to be established, and these need to be discussed with the appropriate stakeholders. Paediatric patients may often be managed in adult units, and thus, there may need to be members of both teams present to facilitate management. Post-transplant follow-up and long-term care
These involve clinical and biochemical follow-up of graft function and careful drug-level monitoring. Long-term care needs to address adherence, complications of immunosuppression, and importantly, transition of adolescents to adult services. Sustainability
Transplant programmes are frequently initiated by enthusiastic well-trained surgeons, but in 670
order for a programme to be successful, there needs to be a multidisciplinary team approach to the care of a transplant recipient with national government and local centre administrative support. Transplantation, particularly long-term care, is expensive, and the responsibility of these costs needs to be discussed at national level so that all citizens have potential access to transplantation. There needs to be on-going training of medical, paramedical, and nursing staff as well as adequate funding of individuals within a transplant team and transplant centres. Transplant centres together with government support need to commit to lifelong care of transplant recipients and secure access to lifelong immunosuppression. Special problems facing paediatric transplant programmes in Africa
There are often wide socio-economic disparities within Africa including South Africa with differences in the level of facilities and medical care available in rural and urban areas as well as between the state and private sector. Transplant assessment
Children are frequently referred late for transplant assessment as transplantation is still seen as a last resort. These children are frequently malnourished with severe failure to thrive and have multi-organ involvement. Socio-economic factors play a crucial role in the potential success of transplantation. Parents are frequently unemployed, may be caring for many other children or other family dependants and rely on child support grants. Children and families living in rural areas often have no electricity, inadequate sanitation and water supply. They may be reliant on pit toilets, have no running water, and are dependent on collecting water from rivers. Even those living in urban areas may live in informal settlements and rely on shared amenities such as communal taps and toilets. Not infrequently, these families may not have enough food for all meals which also affects how the immunosuppressive drugs are given, that is, drugs should be taken with meals. The burden of infectious disease such as tuberculosis (TB), viral infections (hepatitis B and C, HIV), malaria, and parasitic infections is high in many African countries and may preclude a child from transplantation. This also increases the potential risk of transmission of infections from the donor, including HIV, hepatitis B and C, schistosomiasis, strongyloides, and Chaga’s disease. This is further exacerbated
Challenges for paediatric transplantation
if access to appropriate and accurate infectious screening of the recipient and donor is not possible. Hepatitis B is endemic in Africa and the presence of occult hepatitis B in the donor still carries the risk of transmission and development of de novo hepatitis B, especially in liver transplant recipients (11, 12). In TB endemic regions, disseminated and extrapulmonary cases are being reported in transplant patients (13, 14), and Isoniazid prophylaxis should be considered. TB drugs such as rifampicin, which are metabolized by the cytochrome p450 system, significantly lower calcineurin inhibitor levels, and thus, higher doses are required with accompanying increased costs and increased risk of graft rejection if the dosage of calcineurin inhibitors is not appropriately increased. Post-transplant infections are important causes of morbidity and mortality post-transplant (15). CMV and EBV infection is endemic in Africa (16, 17) and children are infected with EBV early in life, usually seroconverting by age of three yr (18). These infections can trigger rejection of the transplanted organ and increase the risk of post-transplant lymphoproliferative disease. There needs to be on-going intensive medical care and nutritional support of children awaiting transplantation. Access to medical care is frequently a problem. Children and their families often live in rural areas, and it is important to establish the distance to the local clinic, district hospital, and tertiary centre and whether they have appropriate transport. Hospital funded transport for follow-up visits may not be available, and exorbitant taxi costs may be incurred as both carer and patient are charged. One needs to know the level of medical care available at their nearest health facility – can medical queries be correctly answered and can graft function and immunosuppressive drug levels be monitored; is there access to immunosuppression; and can they be admitted for medical management of complications. Many potential transplant recipients from rural areas within developing countries may live 1000 km from the nearest transplant centre, making it essential to assess whether the child and the family can temporarily relocate (often for many months at a time) to the transplant centre whilst awaiting transplant and until they are stable enough to return home. Post-transplant care
There is frequently a single transplant centre for the whole country. The transplant recipient is a
patient for life, requiring monitoring of graft function and management of long-term complications. Patients frequently return home where there is a lack of a 24-h medical facility. There is usually no dedicated post-transplant clinic or even a dedicated medical caregiver. Communication with the transplant centre on the recipient’s return home is frequently erratic. These problems need to be addressed pre-transplant so that recipients can be selected appropriately and referring medical caregivers informed of their responsibilities in shared medical care both pre- and post-transplantation. The transplant centres need to identify contact medical personal in referring hospitals and establish modes of communication either telephonically or using newer modalities such as email or texting (SMS) to ensure successful long-term follow-up of transplant recipients. Adolescents
“Normal” teenage behaviour and issues of noncompliance play a significant role in resource poor regions as these young people may often only have one “chance” at an organ transplant due to the shortage of organs and these patients not being seen as a “good” investment for retransplantation compared with more mature adult patients. Transition programmes from paediatric to adult services may also not exist (4). Donors
In many countries in Africa, the access to braindead heartbeating donors is limited for a number of reasons including religious, cultural, lack of legal recognition of brain death, but also importantly lack of support for transplantation from medical staff and hospital administrations. Promulgation of legislation regarding organ donation and transplantation may be necessary before a transplant programme can be developed. The majority of African countries rely on living-related donation, and there needs to be detailed protocols in place to ensure adequate screening of and long-term follow-up of livingrelated donors. In addition, many proposed donors may be single parents who are the solebread winners and thus are financially dependent on being able to perform their jobs and not having prolonged periods of sick leave. There is often no organized network for organ sharing, making urgent transplantation and re-transplantation difficult or even impossible. Frequently, private and state programmes compete for donors and the poor are further disadvantaged. 671
Spearman and McCulloch Transplant tourism and organ trafficking
In countries where there is wide socio-economic disparity, limited access to transplantation and lack of legal legislation on organ donation, there is always the risk of organ trafficking and transplant tourism. Fortunately, most countries have now endorsed the Istanbul Declaration on organ trafficking and transplant tourism (19–21). In countries with no established transplant centres, parents either independently or as part of an official government arrangement travel abroad as donor–recipient pairs for living-related transplantation. Common destinations include India, Pakistan, Tunisia, and South Africa. Unfortunately, there is often inadequate oversight with regard to establishing whether the donor and recipient are related or known to each other, and to the safety of the recipient and donor. The recipients and their donors may return to their home countries very soon posttransplantation often with complications and in some cases with very little medical information about what happened peri-operatively and without a protocol for post- transplant care or ensured access to immunosuppression. Ethical considerations
In order for there to be equitable access to transplantation, there needs to be state-funded programmes. However, in African countries with limited health resources, the governments need to exercise responsible stewardship and direct their limited health budgets to the eradication of malaria, HIV/AIDS, tuberculosis, gastroenteritis, and malnutrition and ensure appropriate prophylactic immunization of the population as well as community health education programmes. It is therefore not appropriate that every country in Africa has its own transplant programme, but it is important to identify and support countries that have the capacity and could act as official referral centres for living-related transplantation and as centres to train medical staff in the post-transplant care of transplant recipients. In July 2013, GAT, a partnership between TTS and the WHO, for the worldwide promotion of organ donation and transplantation activities held a symposium in Durban, South Africa, to assess the need for and obstacles to transplantation and obtaining government support in sub-Saharan Africa and to develop/promote mentoring schemes with well-established transplant programmes. Eleven countries based on their need and ability to develop a transplant programme were invited to participate (Cameroon, Ethiopia, Ghana, Kenya, Malawi, 672
Nigeria, Rwanda, Senegal, Sudan, Tunisia, and Zambia) (2, 3). A major obstacle to sustainable transplantation is the cost of long-term immunosuppression. National governments together with the International Transplant Community should consider lobbying pharmaceutical companies collectively for Africa for access to affordable immunosuppressive drugs including low-cost generic drugs in the same way as anti-retroviral therapy was provided for Africa. The role of scientific organizations
There has been an increased awareness by scientific and professional societies, especially in developed countries of their responsibility to assist in ongoing education and training in developing countries. In Africa, some specific examples have included the ESPGHAN which has been running twice yearly one-wk workshops and have twinned with pharmaceutical sponsors to fly participants from various parts of Africa for training in these fields. This increases the basic knowledge and sets the foundation for eventual transplantation. Similarly, renal societies such as the IPNA and their adult counterpart the ISN have provided 1– 2-yr fellowship training programmes to establish knowledge in renal disease including the assessment and follow-up of renal transplant patients. The ideology has been to train African fellows in centres of excellence in Africa which has not only improved understanding of local disease pathologies, but also limited the number of fellows who travel to train in developed countries, never to return to Africa. More recently, several organizations have worked together as an initiative called Saving Young Lives (including IPNA/ISN/ISPD and Sustainable Kidney Care Foundation) to provide one-wk training courses in nephrology, specifically hands-on approaches to initiating acute dialysis with pharmaceutical companies providing supplies with a view to later developing chronic dialysis. Finally, following the successful establishment of Adult Sister Centre Programmes such as those offered by ISN and TTS in terms of manpower and specifically surgical training, whereby a centre from a developing country and developed country twin for support – including visits over a 1–3-yr period depending on level of exchange (Category A, B, and C from basic support [C] to highest level of support [A]). Paediatric organizations such as IPNA and IPTA have implemented similar programmes (personal communication
Challenges for paediatric transplantation
MI McCulloch – currently on Council of IPNA as Sister Centre Chair and IPTA Council). Membership reduction for developed countries has also been implemented by many organizations, and in some cases, this has been done in conjunction with local organizations to allow these to be established, for example, currently 50% IPNA registration is paid to the International society and 50% goes to the local AFPNA. Use of modern technology such as online training and webinars further enhances these scientific organizations’ support. Recommendations for establishing paediatric transplant programmes in Africa
Established transplant programmes in Africa (South Africa and Egypt) have usually first established a renal dialysis programme, ensured that the required complex infrastructure is in place and then started with an adult renal transplant programme before embarking on paediatric renal transplant programmes. The infrastructure required for deceased organ donation is significant: legal and cultural recognition of brain death, independent determination of the neurological criteria for brain death in an intensive care unit in a patient on mechanical ventilation, tissue typing and cross-matching facilities, an organ procurement programme and an on-call surgical team (3). Renal transplantation programmes should start with livingrelated programmes and once the appropriate infrastructure is in place, consider deceased donation. Once a successful renal transplant programme is in place, a country can then assess the need to establish their own liver, heart, lung, pancreas, and intestinal transplant programmes. Establishment of these more complex solid organ transplant programmes will not be appropriate for most African countries, but the establishment of a successful renal transplant programme will enable the transplant medical fraternity to follow up other solid organ transplant recipients as part of shared care. To achieve an equitable balance, governments may need to institute funding streams for various levels of health care: primary, secondary, and tertiary health care with resultant rationing at each level, for example, limited number of renal dialysis slots according to budget. This also requires the government sector to centralize tertiary services to allow an adequate volume of high-cost and complex procedures such as transplantation to be performed with adequate skill and expertise in only three or four
centres around a country initially depending on the population and geographic area. It is important to establish transplant donor and recipient registries to ensure transparency by documenting transplant activity in the private and state sector, waiting lists, short- and longterm outcomes as well as donor morbidity and mortality. This registry data also provide an objective basis for advocacy for transplantation. The establishment of organ donor foundations is important to educate and increase public awareness about the need and benefits of organ donation. The International Transplant Community should play an ongoing active role in the education and training of the transplant community in Africa and provide a forum at international meetings where African transplant programmes can present their outcomes. Conclusion
Successful transplant programmes have been established in Africa (2, 12, 22–28), despite major obstacles. The establishment of transplant programmes requires careful planning with national government support, and a multidisciplinary team approach with mentoring of staff is important. It is often beneficial to share resources and skills between adult and paediatric programmes as well as regional networking (22, 23, 28, 29). Twinning with established overseas programmes helps to improve the skills base, but the ultimate aim should be to enable local transplant programmes to be self-sufficient in all aspects of medical and surgical care of the transplant recipient. Private–public partnerships enabling sharing of skills base and resources and equitable sharing of donors should be encouraged. Secure access to lifelong medical care and subsidized immunosuppression (not just short term for the first 2–3 yr), so that all citizens within a country have potential access to transplantation, is crucial before embarking on a transplant programme. Although expensive and labourintensive, successful transplant programmes have the added benefit of raising the general level of medical and surgical care in a transplant centre, which not only benefits other patients, but also helps to retain highly skilled medical personnel. References 1. WHO. Global Observatory on Donation and Transplantation. Available at: www.transplant-observatory.org (accessed 2 May 2014).
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Spearman and McCulloch 2. REPORT OF THE GLOBAL ALLIANCE FOR TRANSPLANTATION WORKSHOP. Awaiting publication personal communication ELMI MULLER. 29–30 July 2013. Durban, KwaZulu-Natal, South Africa. 3. MULLER E, WHITE S, DELMONICO F. Regional perspective: Developing organ transplantation in sub-Saharan Africa. Transplantation 2014: 97: 975–976. 4. HARDEN PN, WALSH G, BANDLER N, et al. Bridging the gap: An integrated paediatric to adult clinical service for young adults with kidney failure. BMJ 2012: 344: e3718. 5. QUAK SH. Liver transplantation in the developing world. Curr Opin Organ Transplant 2009: 14: 540–543. 6. AKOH JA. Renal transplantation in developing countries. Saudi J Kidney Dis Transpl 2011: 22: 637–650. 7. GOPCEVIC A, VUCIC M, LOVRENCIC-HUZJAN A, et al. Increased donor rate at Sestre milosrdnice University Hospital. Acta Clin Croat 2009: 48: 319–324. 8. SPASOVSKI G, BUSIC M, PIPERO P, et al. Current status of transplantation and organ donation in the Balkans–could it be improved through the South-eastern Europe Health Network (SEEHN) initiative? Nephrol Dial Transplant 2012: 27: 1319– 1323. 9. ZIVCIC-COSIC S, BUSIC M, ZUPAN Z, et al. Development of the Croatian model of organ donation and transplantation. Croat Med J 2013: 54: 65–70. 10. MOLYNEUX E, O’HARE B. The value of including global health in the training of health professionals. Arch Dis Child 2013: 98: 840–842. 11. LEE KH, CHUN TW, LIM SG, et al. Risk for de novo hepatitis B from antibody to hepatitis B core antigen-positive donors in liver transplantation in Singapore. Liver Transplant 2001: 7: 469–470. 12. BOTHA JF, SPEARMAN CW, MILLAR AJ, et al. Ten years of liver transplantation at Groote Schuur Hospital. S Afr Med J 2000: 90: 880–883. 13. BOUBAKER K, GARGAH T, ABDERRAHIM E, BEN ABDALLAH T, KHEDER A. Mycobacterium tuberculosis infection following kidney transplantation. Biomed Res Int 2013: 2013: 347103. 14. HSU MS, WANG JL, KO WJ, et al. Clinical features and outcome of tuberculosis in solid organ transplant recipients. Am J Med Sci 2007: 334: 106–110. 15. ULLAH K, REZA S, AHMED P, et al. Posttransplant infections: Single centre experience from the developing world. Int J Infect Dis 2008: 12: 203–214.
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16. KRECH U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ 1973: 49: 103–106. 17. ADJEI AA, ARMAH HB, GBAGBO F, BOAMAH I, ADU-GYAMFI C, ASARE I. Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa. BMC Infect Dis 2008: 8: 111. 18. BIGGAR RJ, HENLE W, FLEISHER G, BOCKER J, LENNETTE ET, HENLE G. Primary Epstein-Barr virus infections in African infants. I. Decline of maternal antibodies and time of infection. Int J Cancer 1978: 22: 239–243. 19. Participants in the International Summit of Transplant Tourism and Organ Trafficking, Convened by The Transplantation Society and International society of Nephrology. The declaration of Istanbul on organ trafficking and transplant tourism. Clin J Am Soc Nephrol 2008; 10: 1227–1231 20. STEERING COMMITTEE OF THE ISTANBUL SUMMIT. Organ trafficking and transplant tourism and commercialism: The Declaration of Istanbul. Lancet 2008: 372: 5–6. 21. AKOH JA. Key issues in transplant tourism. World J Transplant 2012: 2: 9–18. 22. SPEARMAN CWN, MCCULLOCH M, MILLAR AKW, et al. Liver transplantation at Red Cross War Memorial Children’s Hospital. S Afr Med J 2006: 96: 960–963. 23. MCCULLOCH MI, GAJJAR P, SPEARMAN CWN, et al. Overview of a paediatric renal transplant programme. S Afr Med J 2006: 96: 955–959. 24. MILLAR AJ, HAMZA AF. Liver transplantation in an African setting. Semin Pediatr Surg 2012: 21: 164–171. 25. KHALAF H, EL-METENI M, EL-SEFI T, et al. Evolution of living donor liver transplantation in Egypt. Saudi Med J 2005: 26: 1394–1397. 26. HADDIYA I, RADOUI A, BENAMAR L, et al. Ten years of renal transplantation in a Moroccan hospital: Results and constraints. Transplant Proc 2012: 44: 2976–2981. 27. BARDI R, CHERIF M, GOUCHA R, et al. Kidney transplantation: Charles Nicolle Hospital experience. Transplant Proc 2009: 41: 651–653. 28. LOVELAND JA, GOVENDER T, BOTHA J, BRITZ R. Paediatric liver transplantation in Johannesburg: Initial 29 cases and prospects for the future. S Afr Med J 2012: 7: 233–236. 29. SPASOVSKI G, DOHCEV S, STANKOV O, et al. The improvement in kidney transplant program in R. Macedonia – what are the clues? Prilozi 2013: 34: 9–13.
