Non-Communicable Diseases and Sickle Cell Disease

Transcription

1 Non-Communicable Diseases and Sickle Cell Disease le - Professor Obiageli E. Nnodu Department of Haematology & Blood (MD, Transfusion Director, Centre for Sickle Cell Disease Research and Training (CESRTA) University of Abuja Abuja, Nigeria Wednesday June 28, 2017 FWACP Lab Med)

2 Number of Newborns with Sickle Cell Anemia in Each Country in Piel FB et al. N Engl J Med 2017;376: Add a footer

3 Nigeria has the Biggest Burden of SCD Global prevalence of sickle globin gene Nigeria has about million SCD patients and over 100,000 HbSS births /yr. (NDS 1999, 19 per 1000 population) Nigeria Babies born with SCD /yr

4 Real Burden of Sickle Cell Disease in 2017? No objective survey since Current figures based on estimate of gene frequencies and mathematical modelling.

5 Introduction Sickle haemoglobin becomes liquid crystals in conditions of low oxygen tension causing the red blood cells to assume a rigid sickle shape with consequent haemolysis leading to a plethora of downstream pathophysiological effects. Telen, M. Blood : ; 5

6 Clinical Complications Infection/Sepsis Splenic Sequestration Ischemic Stroke Dactylitis Pediatrics VOE ACS Gallstones Priapism Fe Overload Aplastic Crisis Pulmonary Hypertension Nephropathy AVN Leg Ulcers Chronic Lung Disease Multi Organ Failure Hemorrhagic Stroke Adults The underlying mechanisms result in age -dependent clinical complications of SCD. 6

7 Common Clinical Complications of Sickle Cell Disease. Piel FB et al. N Engl J Med 2017;376: Piel,

8 Interventional Options for SCD HYDROXYUREA IS THE ONLY DRUG LICENSED FOR USE IN SCD Haematopoietic stem cell Transplant Steinberg, 2008 Gene Therapy At the molecular level treatments are designed to : 1. Reduce adhesiveness ( Anti selectins, HU) 2. Reduce the ability of HbS to form liquid crystals ( HbF, HU, Metformin) 3. Reduce the HbS concentration (Blood transfusion) Thus HU and Blood Transfusion are disease modifying therapeutic agents for SCD. 8

9 Treatment 1. Preventive 2. Therapeutic 3. Curative : Stem Cell Transplantation, Gene therapy 4. Health Maintenance Management of Acute Complications 1. Vaso occlusive crisis 2. Anaemia 3. Acute splenic sequestration 4. Stroke 5. Acute chest syndrome 6. Priapism Management of Chronic Complications 1. Leg ulcers 2. Pulmonary hypertension 3. Avascular necrosis of femoral head 4. Renal complications 9

10 Recommended Examinations to be Performed Annually Age (years) Physical examination Transcutaneous O 2 sat Laboratory tests* Assessment of adherence to treatment and appointments Transcranial Doppler ultrasound Liver/gallbladder ultrasound Academic performances Pulmonary function tests Hip X-ray Electrocardiogram Ophthalmological evaluation** * Complete blood count, liver profile, électrolytes, blood urea nitrogen, creatinine, microalbuminuria, serum ferritin if transfused, calcium metabolism, parvovirus B19 serology until positive. 10 ** From 6 years onwards. if Hb SC disease. De Montalembert M, et al. Am J Hematol. 2011;86:72-5.

11 Current Status of SCD Treatment and Infrastructure in Nigeria 1. Current Management Practices, 2. Blood Transfusion Practices Add a footer

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13 Distribution of Institutions Offering Tertiary Care Services in the Nigerian SCD Network No of Haematologists varies from 1-10 Hospital Beds All provide outpatient care in SC clinics. Emergency Care in A&E or Day Care Units. 13

14 SCD Screening / Diagnostic Facilities in Nigerian Centers *Some centers have acquired more facilities since 2014 Galadanci N, et al. International Health, Oct 2014; doi: /inthealth/iht022 14

15 Procedure For Follow-Up and Initial Counselling When a diagnosis is confirmed: 1. Initial counselling and parent education is provided by the physician but some centres have trained counsellors 2. Descriptive location is requested for address with important landmarks and contact telephone. 3. Pilot mhealth survey in Katsina, Ife and Abuja show 95.6 % mobile telephony penetration in rural areas. 4. Detailed physical examinations and baseline investigations are performed to phenotype the patient and for follow up monitoring at clinics at intervals of 2-12 weeks depending on the individual patient s condition 15

16 SCD Patient Management in Nigerian Centers Centre Adult Paediatric Total No of Patients Medical Records Data base Drugs given- Folic acid Malaria prophylaxis Penicillin Hydroxyurea 16 Galadanci N, et al. International Health, Oct 2014; doi: /inthealth/iht022

17 SCD Patient Management in Nigeria Pain Rx: stepwise analgesia with paracetamol/nsaids (mild) => DF118 (moderate) => pentazocine/morphine (severe). Fever: Following infection screen, anti-malarials & antibiotics Other Care Provided in Some Centers 1. Stem Cell Transplant for severe SCD; 3 pts so far in UBTH 2. Regular transfusion to prevent recurrent stroke 3. Oral iron chelation with deferasirox (Asunra/Exjade). 4. Various approximations to comprehensive care of SCD 17

18 Hydroxyurea Therapy Despite the evidence, most centres do not use hydroxyurea. There is still some concern about its safety although the capacity to monitor its treatment is there. We encourage physicians to offer HUT after baseline investigations and careful explanation of possible side effects to parents/patients and allow them to make the decision. There are concerns about paucity of clinical trials of HUT in the African continent and the fact that pharmacogenomic studies of HU have not been carried out on African populations. Many feel that there should be therapeutic drug monitoring of patients while on HU therapy. 18

19 SCD Patient Management in Nigeria Pain Rx: stepwise analgesia with paracetamol/nsaids (mild) => DF118 (moderate) => pentazocine/morphine (severe). Fever: Following infection screen, anti-malarials & antibiotics Other Care Provided in Some Centers 1. Stem Cell Transplant for severe SCD; 3 pts so far in UBTH 2. Regular transfusion to prevent recurrent stroke 3. Oral iron chelation with deferasirox (Asunra/Exjade). 4. Various approximations to comprehensive care of SCD 19

20 Guidelines Available Observations from the SCD Network papers: 1. Inconsistent standard of care 2. Practices dependent on facilities and resources available in each centre and what the patient can afford. 20

21 Blood Transfusion in SCD Indications for blood transfusion in SCD with moderate to strong quality of evidence: 1. Simple blood transfusion for acute anaemic episodes and perioperative period. 2. Chronic transfusion program for primary and secondary stroke prevention and the prevention of silent cerebral infarcts Blood transfusion also given for 1. Recurrent episodes of acute chest syndrome 2. Management of severe recurrent pain episodes 21

22 Blood Transfusion Services for SCD Blood Transfusion Services ought to be centrally coordinated with Clear indications for blood transfusion according to strict protocols Pretransfusion testing, pathogen inactivation and leuco-depletion Different modalities and components ought to be available: simple, manual exchange, automated exchange, RCC, PC, LD RCC Post transfusion surveillance, infections, antibody testing for alloimmunization, iron stores However gaps in skill and infrastructure in resource limited countries warrant attention to other treatment modalities for stroke prevention. Other treatment modalities (SPIN Trial in Kano, Nigeria). 22

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24 Blood Screening Practices 24

25 Posttransfusion Monitoring 25

26 Summary of Blood Transfusion Practices for SCD in Nigeria Current efforts of Nigerian public hospitals to provide safe blood and CTT fall short of best practice. No centrally coordinated blood transfusion service Most hospitals run a family replacement donor system Red cell transfusions for SCD patients are not leukocyte-depleted Extended phenotype matching is not available Testing of donor blood for HbS is not done routinely Exchange blood transfusions are mostly manual Most centres do not have apharesis machines Haemovigilance system is not in place Alloantibody screening is not done routinely Only serum ferritin is available to monitor iron overload Access to iron chelators is limited and expensive 26

27 Current Model of Care for SCD in Nigeria Hospital based with poor coverage of affected individuals. Not accessible to majority of the population ( Total of 23,750 in clinical centres cf to expected no of m ) 27

28 Current treatment for VOC Episodes in SCD patients in Nigeria? From National Guidelines Add a footer

29 Guidelines 29

30 Treatment of Pain Crisis in SCD 30

31 Impact of National Health Act and Other National Policies on SCD in Nigeria Providing a roadmap for stakeholder engagement and action. Most people are unaware of document and not working towards its implementation.

32 What are Possible Areas of Partnership With Pfizer in Addressing the Burden of SCD in Nigeria? Interventions for the control of SCD include NBS and prophylaxis for infection (ASH NBS Consortium) Training health care workers in the use of guidelines Generating data on actual disease burden support NCD Step +Sickle POCT, 27,2750, plus blood in EDTA for analysis of variant Partnership for clinical trials. (Platform available within the 39 Clinical Centres under the SCSSN to support clinical trials Support proof of concept pilot research project in GAC.

33 Basic Interventions for the Control of Sickle Cell Disease in Resource Limited Settings 1) Raise public awareness about SCD 2) New-born screening 3) Screening for sickle cell disease at primary health care centres 4) Genetic counselling of individuals with abnormal haemoglobin i.e. AS, AC SS, SC. 5) Registry of patients with SCD for prospective follow up 6) Prophylaxis for infection, pneumococcal vaccines, oral penicillin, use of insecticide treated bed nets and anti-malarial 7) Health maintenance at PHC (Comprehensive care through integration into Secondary and Tertiary Health Care Centres) 8) Nutrition 9) Education of patients and care givers about sickle cell disease including what to do in acute conditions before coming to the hospital. 10)Optimal hydration by teaching the patients to drink enough fluids to make their urine clear and whitish without yellow colour Current Advances in the Management of SCD 33

34 Collaborating Centres 1. Ahmadu Bello University Zaria, Kaduna State 2. Aminu Kano University Teaching Hosp, Kano, Kano State 3. Benue state University, Makurdi, Benue State 4. Bingham University, Karu, Nassarawa State, Nigeria 5. Ekiti State University, Teaching Hospital, Ado Ekiti, Ekiti State 6. Enugu State University of Science and Technology Teaching Hospital, Parklane, Enugu State 7. Federal Medical Centre, Asaba, Delta State 8. Federal Medical Centre Bida, Niger State 9. Federal Medical Centre Ido-Ekiti, Ekiti State 10. Federal Medical Centre Keffi, Nassarawa State 11. Federal Medical Centre Birnin Kebbi, Kebbi State 12. Federal Medical Center, Owerri, Imo State 13. Federal Teaching Hospital, Abakaliki, Ebonyi State 14. Federal Teaching Hospital, Gombe, Gombe State 15. Gbagada General Hospital, Lagos, Lagos State 16. General Hospital Katsina, Katsina State 17. Ifako-Ijaiye General Hospital, Lagos, Lagos State 18. Ladoke Akintola University of Technology, Ogbomoso, Oyo State 19. Lagos State University Teaching Hospital, Lagos, Lagos State 20. Lagos University Teaching Hospital, Lagos, Lagos State 21. Massey Street Children s Hospital, Lagos, Lagos State 22. Murtala Muhammed Specialist Hospital, Kano, Kano State 23. National Hospital, Abuja 24. Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State 25. Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State 26. Sickle Cell Foundation, Lagos, Lagos State 27. University College Hospital, Ibadan, Oyo State 28. University of Abuja Teaching Hospital, Gwagwalada, Abuja 29. University of Benin Teaching Hospital, Benin, Edo State 30. University of Calabar Teaching Hospital, Calabar, Calabar State 31. University of Ilorin Teaching Hospital, Ilorin, Kwara State 32. University of Maiduguri Teaching Hospital, Maiduguri, Borno State 33. University of Nigeria Teaching Hospital Enugu, Enugu State 34. University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State 35. University of Port Harcourt, Port Harcourt, Rivers State 36. University of Uyo Teaching Hospital, Akwa Ibom State 37. Uthman Danfodio University Teaching Hospital, Sokoto, Sokoto State 38. Wesley Guild Hospital, Ilesa, Osun State 39. Zankli Medical Centre, Abuja

35 Compared POCT with CAE and HPLC in adults and children attending GTC in Gwagwalada Area Council of the FCT. SickleSCAN showed good sensitivity, specificity and test efficiency and could be used as viable screening tool that can easily be applied in community-based screening for early diagnosis of SCD with little expertise and low cost. Nationwide acceptability and feasibility of POCT in screening in the zones of the Sickle Cell Network.

36 Validation of POCT. Comparison with CAE and HPLC in adults and children attending GTC in Gwagwalada Area Council of the FCT. With good sensitivity, specificity and test efficiency. Nationwide acceptability and feasibility of using POCT in screening in the zones of the Sickle Cell Network. Majority prefer a test that would cost less than a dollar

37 Comments Slides to answer some of the questions raised during the different presentations. Add a footer

38 Sickle Cell Disease in Bahrain Comprehensive education program to increase public awareness of the disease and how to avoid them. (Presentations, leaflets and booklets) Media Key opinion leaders Schools and other public places National budget Ministry of Health/ Education/ Bahrain Hereditary Anaemia Soceity In 24 years, Bahrain reduced the prevalence of SCD in newborns from 20/1000 to 6/1000 representing 60-70% decline.

39 Attitude Towards Prenatal Diagnosis of Sickle Cell Disease and New Born Screening in Nigeria

40 Responses of Subgroups Knowledge of cause of SCD [Frequency (%)] Among the Categ0ry of Respondents Responses HCW Hb AS/AC Parent SCD patient Student SCD patient Blood disorder 18 (100) (82) 342 (85) 72 (86.5) (82.3) Contagious 0 1 (1.2) 5 (3.8) 15 (3.9) 6 (7.1) Inherited from mother 1 (5.6) 3 (3.3) 7 (5.11) 9 (2.3) 3 (3.5) Inherited from father 0 2 (2.2) 6 (4.4) 7 (1.7) 2 (2.3) Inherited from both parents 18 (100) 87 (91.6) 117 (84.2) 374 (92.4) 78 (88.6) It is Gods will 5 (29) 32 (34.8) 55 (40.4) 48 (12) 37 (42.1)

41 Support for Prenatal Diagnosis for SCD Responses HCW HbAS/AC Parent SCD patient Student SCD patient Yes 17 (94) 75 (76.5) 104 (72.7) 333 (79.3) 64 (72.7) No 1 (5.5) 15 (15.3) 30 (20.9) 50 (11.9) 18 (20.5) Not sure 0 8 (8.6) 9 (6.3) 37 (8.9) 6 (6.8) Support for NBS was higher than for NBS Support for NBS for SCD HCW HbAS/AC Parent SCD Student patient SCD patient Responses Yes 17 (94.4) 96 (96) 122 (85.9) 394 (94) 83 (94) No 1 (5.6) 3 (3.0) 12 (8.5) 14 (3.32) 2 (2.7) Not sure 0 1 (1.0) 8 (5.6) 11 (2.6) 3 (3.4)

42 Multisectoral Collaboration MDGSCC Sickle Cell Support Soceity of Nigeria FMOH FMEd Clinical Centres NPHCDA/ NIPRD