Status of Primary Immunodeficiencies in Africa

1. Status of Primary Immunodeficiencies in Africa James Chipeta(BSc.<HB>,MBChB,PhD) Associate Professor of Paediatrics & Clinical Immunology, University of Zambia School of Medicine, Department of Paediatrics and Child Health, University Teaching Hospitals –Lusaka Children Hospital, Lusaka, Zambia 2019 Kenya Paediatrics Association (KPA) Annual Scientific Conference, A Project –Kenya (The Child with too many infections – are we missing something?), 9-12th April, 2019, SarovaWhitesands Hotel, Mombasa, Kenya

2. Disclosures None

3. A Snap Literature Review of Current Status of Primary Immunodeficiencies on the African Continent with special focus on Challenges of PID Case Management amidst some Shed of Hope

4. Presentation Overview • Background • The World ‘Single Story’ Perception of Africa and the Backdrop of high burden of Infectious Diseases • Vision 2030 and a Continent on the Rise • Highlights of the Burden of PID –Global and on the African continent • PID disease Burden –Global and Local • Challenges of Case management of PID in Africa • What is the evidence-based prescription to the challenges? • Highlights on the way forward – Some shed of Hope • PIDs management is possible on the continent • Some Evidence-Based solutions – The IPOPI’s Principles of PID Care • Discussion Chipeta J et al.

5. BACKGROUND Common World Perception of Africa Diseases Poverty Hunger Wars Chipeta J et al.

6. Global population distribution Chipeta J et al. Source: www.worldmapper.org

7. Global distribution of Malaria (The biggest cause of death for African children <5yrs ) Chipeta J et al. Source: www.worldmapper.org

8. Global distribution of HIV Chipeta J et al. Source: www.worldmapper.org

9. Global distribution of TB Source: www.worldmapper.org

10. So why bother about PIDs in Africa? The Global Vision 2030: Attaining all the 17 Sustainable Development Goals without leaving anyone behind.

11. Background II: Sub-Sahara Africa and the Double Burden of Communicable and Non Communicable Diseases • Malaria • HIV/AIDS • Tuberculosis • Neglected tropical Diseases (NTDs or ?PDD) • High poverty levels • Underreported high NCDs Burden • Rich in Natural Resources • Rising Economies Chipeta J et al.

12. ‘Africa is rising’ The world’s fastest growing continent March 2, 2013

13. Double Burden of Communicable & NCDs in SSA: Current Situation (Dalal S et al.-2011 and WHO: Projections of Global Burden of Disease 2002-2030) Chipeta J et al.

14. Highlights of the Burden of PID –Global and on the African continent

15. PID “Worldmapper ?” • Primary immunodeficiency diseases worldwideBousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova JL, Abel L.J ClinImmunol. 2013 Jan;33(1):1-7. doi: 10.1007/s10875-012-9751-7. Epub 2012 Jul 31 six million people with PID PID -more common than haemophilia/ cystic fibrosis /Huntington’s disease – but not a “UNIFIED “Disease (IDF, 1995, first national survey of primary immune deficiency diseases in America)

16. Primary immunodeficiency diseases worldwideBousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova JL, Abel L.J ClinImmunol. 2013 Jan;33(1):1-7. doi: 10.1007/s10875-012-9751-7. Epub 2012 Jul 31 • World Mapper estimates suggest that six million people may be living with a PID worldwide, whereas only 27,000-60,000 have been identified to date (all national registries and the Jeffrey Modell Centers Network, respectively). • For Europe, upper estimate was 638,000 cases, and 20,000 cases are currently registered (3.13 %: Nizar Mahlaoui et al, 2017). • In Africa, up to 902,631 (650,000 current estimates) people may have a PID, whereas only a few thousand cases are currently registered with the majority of the countries not having any PID records/registry. • PIDs on existing registries are prevalent not only in children, but also in adults, who are strongly underrepresented on registries.

18. Status of PIDs on the African Continent: The Challenges of Case Management Amidst Some Shed of Hope

19. Ideal Rights of a Child with PID Condition The best scenario for every child with a PID • An assessment by an appropriately trained paediatric specialist • A prompt referral to a paediatric centre as needed. • The best available care is accorded to such a child

21. Current State and Advances in Primary Immunodeficiency Care (Nizar Mahloui, et al, 2017) • General Awareness about PIDs remains patchy world-wide • Remarkable improvement in the understanding of the disease pathophysiology with robust advances in case management (Diagnosis and Treatment) • Greater patient Survival than ever before • Traditional Patient evaluation (History and Physical examination) remain key and critical in PID diagnosis • Diagnoses spans through from improved routine tests such as T-cell receptors excision circle assays incorporated in the Gutherie dried blood spot samples for Newborn screening of SCID to several disease discovery assays • Wider availability of IVG therapy • Improved Human Stem Cell Transplantation services • Prospects of Genetherapy

22. Demystification of the IUIS PID Classification

23. Encountered PID Case Management Challenges on the African Continent Clinical • Low Disease Awareness • Low clinical index of suspicion • Huge patient work load-over crowded with infectious diseases (Difficult differential Diagnosis) • Late Presentation • Human resource (HR)-None/inadequate expertise Diagnostics • None availability of equipment and diagnostic tests • Erratic lab reagents and other diagnostics support (Immagingstudies,etc) • HR issues-lack or inadequate expertise Cross-cutting issues • Poverty • Weak Health Systems

24. Issues Regarding PIDs Management Challenges in Africa Chipeta J et al.

26. Summary of PID Cases seen at UTH: Challenges I (Access to Expert Health Facilities)

27. Summary of the Challenges

28. Do we have any Solutions to the Plight of PIDs in Africa? Chipeta J et al.

29. ASID Goal/Vision ASID as a Professional Society primarily focuses on : • sharing experiences and raising public awareness with regard to the basic and clinical science of PIDs in Africa. • commitment to the promotion of evidence-based management and care of individuals suffering from PID. • seeking, through better and more effective interventions, to uplift the quality of life of PID patients on the African continent.

30. 5th Biennial ASID 2017 Congress Chartered PID Priorities for Africa: Livingston-Victoria Falls, Zambia Awareness Treatment and Care Diagnostics Data Management & Research Advocacy and Public – Private –Partnerships (PPP) Chipeta J et al.

31. Raising Awareness to improve the current status of PID on the Continent: The A Project • 56 African Countries • Grosssundiagnosis and misdiagnosis of PIDs on the continent • Caregivers cannot easily access congresses/resources • Patients have no voice • Urgent need to improve lives of African PID patients • Urgent need to document the African genetic PID landscape

32. Is PIDManagement possible in Africa ? • Yes, very possible: PID is a clinical diagnosis - the power of thorough clinical evaluation (History taking and Physical evaluation) • PID basic management (Diagnosis and Treatment) is possible nearly in every country on the continent • Prof. Aziz’s Phenotypic approach to PID diagnosis • Recognized upcoming centres of excellence in PID management on the continent (Morocco, Tunisia, South Africa, Sudan)

33. Distribution of PIDs Seen at University Teaching Hospital, Lusaka(UTH), Zambia (2006-2018)

34. Available Evidence-Based Solutions: The SIX IPOPI PID Principles of Care I

35. Available Evidence-Based Solutions: The SIX IPOPI PID Principles of Care II

36. Available Evidence-Based Solutions: The SIX IPOPI PID Principles of Care III

37. Acknowledgements The Kenya Paediatrics Association (KPA) and Dr. Angela Migowa ASID Board • Secretary-general and Clinical training : Aziz Bousfiha, ASID Founder • Current ASID President : TandakhaDieye , Senegal • Current and Past Members (Monika Esser -Registry , Brian Eley,RidhaBarbouche, Leila Jeddane, Nadia Kechout, Meriem Ben Ali, MaroufouAlao, NahlaErwa, Wesal Mohammed, Shereen Reda -Awareness, FethiMellouli ) University of Zambia/School of Medicine

38. Thank You

39. Starting with The Call for A.F.R.I.C.A(ASID II Congress Hammameth, Tunisia 2012) • Appropriate awareness • Foster Education of Health Professionals • Research and data collection • Identify through early diagnosis • Comprehensive and appropriate treatment • forAfrica • andAProjects

40. History of JA Project • J Project Highly successful Concept for PID workshop based clinical teaching of LászlóMaródi – model for Eastern Europe • A Project = Daughter Concept planned at IPIC Congress Estoril, Spain November 2013 by Aziz Bousfiiha et al. • AProject then introduced at 100th J Project Meeting , March 2014, Turkey. • 7 A Projects held to date

41. No. 8 ! Uganda A-Project 2nd Sub Saharan A Project, April 2014 Total: Close to 20 Two Recent Ones: • Namibia • Mauritius No. 14 ! Rwanda A-Project

42. The African Society for Immunodeficiencies (ASID) and the A Project Main objectives of ASID : to improve PID awareness and care in Africa. Accordingly the ASID concept of the A-Project initiative is to establish and foster: • PID awareness in Africa • Enhance expertise in the field of PID • Targeting empowering clinical immunologists, paediatricians, neonatologists, physicians and other health care professionals in their own countries.

43. Is PID diagnosis possible in Africa ?PID is a clinical diagnosis – YES !!! The clinical relevance of an abnormal laboratory finding must be based on the clinical history as well as the size of the difference from the normal range.