1. Clinical epidemiology of individuals with SCD using Hydroxyurea at Muhimbili National Hospital 5 th National Quality Improvement Forum on Health & Social Welfare Dr. Elisha Osati Haematology unit Muhimbili National Hospital

2. Introduction: Sickle Cell Disease 1910 – Clinical Description of SCD 1949 – Molecular basis of SCD Environmental, Social and Cultural factors 1910 – Clinical Description of SCD 1949 – Molecular basis of SCD

3. MUSCULOSKELETAL Osteomyelitis AVN esp Hip INFECTIONS Malaria, Bacterial, viral infections HEMATOLOGY Anaemia RBC Aplasia NEUROLOGY Stroke, blindness, seizures All organ systems are affected - End-organ damage Steady-state; Acute episodes; Poor QoL Spectrum of SCD PSYCHOSOCIAL Psychological Social impact CHEST Infection/infarction Pulmonary hypertension GASTROINTESTINAL Splenic sequestration Gall stones VASCULAR Painful crises, Leg ulcers

4. Burden of SCD Burden of SCD in Africa 237, 253 births a year (76%) Global burden of SCD 312,307 births a year

5. SCD in Tanzania 5th country in world with highest birth prevalence: Nigeria, India, DRC, Tanzania, Angola 8,000 to 11,000 SCD infants are born every year in TZ 15 to 18% estimated to have AS.

6. Overall Mortality (per 100PYO ): TZ: 1.9 vs 0.15 vs USA: 0.6 (Makani, Telfer, Quinn) Under 5 Mortality (per 100PYO ): : TZ: 7.3 USA: 0.81 – 3 Childhood Survival for SCD 0%20%40%60%80%100%120% UK USA Jamaica Africa SS Africa Fleming, 1979; Weatherall, 2006;Wierenga, 2001; Quinn 2004;Telfer, 2007

7. Interventional options for SCD Steinberg, 2008 HYDROXYUREA IS LICENSED FOR USE IN SCD

8. Hydroxyurea Hydroxyurea modulates SCD by increased fetal hemoglobin (HbF) as well as by other less understood methods. The increase in HbF in turn reduces the risk of ‘sickling’ events and improves clinical outcomes. 4. Charache S, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995;332(20):1317-22. 5. Ware RE, et al. Hydroxyurea as an alternative to blood transfusions for the prevention of recurrent stroke in children with sickle cell disease. Blood. 1999;94: 3022-3026. 6. Steinberg MH, et al. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Blood. 1997;89: 1078- 1088.

9. Effective Interventions in SCD Trend in Mortality in SCD in the USA by Yanni et al 2009 Newborn screening Manage Infection Comprehensive Care Hydroxyurea

10. Objectives Broad Objective To describe the clinical epidemiology of individuals with SCD using HU at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. Specific Objectives. To determine the proportion of SCD patients on HU. To evaluate indicators for HU use. To evaluate hematological response to HU in SCD. To describe the clinical outcomes of HU in SCD patients.

11. Methods It was conducted from July 2014 to July 2015 at MNH under the SCD programme. Currently programme has about 5000 SCD patients. It was a descriptive cross- sectional study to determine the proportion of patients with SCD who were using HU and to describe the indications for HU use. The second phase was to evaluate the clinical and laboratory outcome of HU use in SCD. We selected age-sex matched SCD patients who were not on HU and were attending clinics as controls during the study period.

12. Sampling procedure Study participants were enrolled every Thursdays and Fridays the 2 days of the Pediatric and adults SCD clinic respectively, patients were also called through mobile phone to remind them to attend the SCD clinic. Enrollment was also done in the wards when SCD patients were admitted. Those identified to ever used HU were scheduled for visit every month. Blood samples for FBP and HPLC were taken at every visit. Analysis was done by the samples collected at the third visit. Analysis was done using SPSS (Statistical Package for Social Science) software version 20. Unpaired t-test was used to compare the variable means.

13. Results The proportion of SCD patients on HU was 1.05% Among SCA patients who were using HU, 37(88.1%) were initiated the therapy at MNH, though only 7(16.7%) of them reported to get HU from MNH, others reported to buy it from the private pharmacies. The starting dose of HU identified was 15mg/kg and the maximum dose was 30mg/kg per oral per day.

14. Results... indications for HU. Indicationsfrequency% Stroke2252.4 Peripheral neuropathy 12.4 Convulsions614.3 Loss of speech12.4 Pain1126.2 Anaemia1.2.4 Total42100

15. Laboratory results SCD on HU (n= 42) SCD not on HU (n = 32) Test statistic Male2418 Age (Years)13.6 ± 1016 ± 11P<0.001 HbF (%)9.8 (±2.4)6.2 (±1.4)P<0.001 Hb (g/dl)7.5 (±0.4)6.8 (±0.6)P= 0.024 MCV (fl)86.7 (±3.5)80.2(±8.2)P<0.001 MCH (pg)29.3(±1.3)24.83 (±3.1)P<0.001 Retics (%)9.4 (±1.8)7.2 (±0.9)P= 0.067 WBC(10^3/µl)11.3 (±1.3)11.5 (±3.2)P= 0.724 PLT (10^3/µl)409.5 (±64.6)412x (±40)P= 0.767

16. Clinical results 76.2% reported to improve after being on HU for at least six months. 90.9% SCD patients with frequent painful crises reported no history of severe painful episodes that required them to visit the hospital as compared to only 37.5% on the control group (P<0.001). 66.7% out of those with CNS events reported that they did not experience convulsions after HU initiation. One patient with severe anemia denied history of BT post HU.

17. Discussion HbF was higher in patients who were on HU and had positive correlation with clinical outcomes and it can be used as an alternative to chronic blood transfusion. This study has shown that HU can improve clinical severity and improve mortality of SCD individuals in Tanzania. Therefore it should be started to all SCD patients who meet the criteria.

18. Recommendations A very small proportion of SCD individuals were found to be using HU. The Govt of Tanzania through MoHSW should make ease availability and accessibility of HU and if possible to be provided in subsidized price. Further clinical trials are required to evaluate more effects of HU in SCA individuals in Tanzania especially in under fives.

19. This is what we want to achieve Integration of SCD in to the health care systems Comprehensive care Newborn Screening Hydroxyurea