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Newborn Screening for Sickle Cell Disease in Africa:
Public health meets reality
Kwaku Ohene-Frempong. MDChildren’s Hospital of PhiladelphiaSickle Cell Foundation of Ghana
13th September 2016
Weatherall, British J Haematol, 2011, 154, 736–744
Annual Global Births of Severe Disorders of HemoglobinTotal number of births* 464,590
SCD
SS 333,929 (83.3)400,986(86.31)
SC 54,736 (13.6)
S β thal 12,321 (3.1)
Thalassemia
β thalβ thal major 23,329 (53.1) 43,917
(69.0) 63,604(13.69)
E β thal 20,588 (46.9)
α thalHb H disease 14,504 (73.7) 19,687
(31.0)Hb Bart’s hydrops 5,183 (26.3)
ISNS 2016: Newborn Screening for SCD in Africa
*80 % born in low and middle income countries
A. Normal red cell B. Sickled red cell
Scanning Electron Micrographs
What is sickle cell disease?
ISNS 2016: Newborn Screening for SCD in Africa
What is sickle cell disease?
• Sickle cell disease (SCD) is a group of inherited
disorders of red blood cells (RBC) characterized by
anemia, vaso-occlusive complications, chronic organ
damage, and reduced survival.
• SCD is caused by the predominant presence in RBC
of sickle hemoglobin (Hb S), instead of the regular Hb
A. Hb S results from a mutation in the beta-
(hemo)globin gene.
ISNS 2016: Newborn Screening for SCD in Africa
Pain!……. the hallmark of sickle cell disease
“10” redefinedHertz Nazaire
ISNS 2016: Newborn Screening for SCD in Africa
Causes of mortality in sickle cell disease
• Mortality is usually due to acute complications such as
infection, acute chest syndrome, stroke, acute multi-
organ failure, and chronic organ failure.
• The leading cause of death in SCD, especially in
young children, is infection.
ISNS 2016: Newborn Screening for SCD in Africa
Development of Functional Asplenia
Age 3 months Age 8 months
99Tc Sulfur colloid Liver-Spleen Scan
Infant with SCD-SS
ISNS 2016: Newborn Screening for SCD in Africa
Infection in Sickle Cell Disease
Development of Functional Asplenia
Age 3 months Age 8 months
99Tc Sulfur colloid Liver-Spleen Scan
Infant with SCD-SS
Infection in Sickle Cell Disease
ISNS 2016: Newborn Screening for SCD in Africa
Causes of Death in SCD-SS (0-10 yr)
(Gill FM, et al, CSSCD: 1995)Overall incidence: 1.1/100 person-yrs
ISNS 2016: Newborn Screening for SCD in Africa
Bacteremia in SCD-SS Disease, CSSCD
Infection in SCD
ISNS 2016: Newborn Screening for SCD in Africa
Age (yr) <3 3-5 6-9 10-19 >20No. pts. 459 571 630 958 983
Person-yr. 752 1025 1333 2843 3480
No. events 60 26 14 18 30
Incidence/ 7,979 2,536 1,050 633 862105 Pr-yr
Deaths 11 1 4 0 2(Zarkowsky,et al. CSSCD; J Pediatr 1986:579-585)
Incidence of Strep. pneumoniae Bacteremia in SCD-SS Disease
Age (yr) <1* 1-1.9 2-2.9 3-3.9 4-4.9 5-5.9
No. pts. 291 342 362 393 430 434
Pt.yrs 188 268 296 334 346 345
No. events 12 17 17 3 5 4
Incidence105 Pr-yr
6,382 6,343 4,696 898 1,445 1,159
US children< 5y (98-99)^
171 214 65 29 16
* 3 patients were younger than 6 months of age(Zarkowsky,et al. CSSCD; J Pediatr 1986:579-585)
Infection in SCD
ISNS 2016: Newborn Screening for SCD in Africa
Improved Survival in Children with SCD
Effect of Newborn Screening for SCD
ISNS 2016: Newborn Screening for SCD in Africa
How many babies are born with SCD?
Piel et al. 2013. Lancet 381:142–51
Estimate of Global Frequency of Sickle Cell Gene
Global Burden of Sickle Cell Disease
Weatherall, British J Haematol, 2011, 154, 736–744
Estimated Annual Sickle Cell Disease Births
Total number of births 400,986
SS 333,929 (83.3)
SC 54,736 (13.6)
S β thal 12,321 (3.1)
Global Burden of Sickle Cell Disease
Newborns with SCD Increasing Globally
Piel et al. (2013) PLoS Med 10(7): e1001484. doi:10.1371/journal.pmed.1001484
2010-2050 Estimated Newborns with SCD-SS
Sickle Region
2010 2050 2010-2050
SS % SS % % change
Global 305,773 100 404,190 100 +32.2
Americas 11,181 3.7 9,628 2.9 -13.9
Arab-India 47,264 15.5 36,540 12.0 -22.7
Eurasia 5,132 1.7 4,478 1.4 -12.7
Southeast Asia 7 0.0 8 0.0 +14.3
Sub-Saharan Africa 242,187 79.2 353,533 83.7 +46.0
ISNS 2016: Newborn Screening for SCD in Africa
Incidence of SCD in Newborns in sub-Saharan Africa
Country No. tested
FAS(AS) %
FAC(AC) %
FS(SS) %
FSC(SC) %
SCD(ALL)
Authors (Year)
Burkina Faso 2,341 7.14 16.67 0.6 1.15 1:57 Kafando et al, ‘05
Togo 385 18.7 8.9 1.0 1.3 1:43 North et al, ‘88
Congo (DRC) 31,204 16.9 - 1.4 - 1:71 Tshilolo, 09
Nigeria 644 20.6 1.1 2.8* 0.2 1:33* Odunvbun, 09
Ghana 255,991 13.35 8.75 0.96 0.81 1:55 Ohene-Frempong MOH, ‘08
USA 1:2,474 Therrell, 08
* Probable overestimate due to low number tested
ISNS 2016: Newborn Screening for SCD in Africa
African Countries with Past or Ongoing Pilot Newborn Screening for SCD
1. Angola 2. Benin (selected)3. Burkina Faso (past)4. Cameroon5. Congo DR6. Congo Republic7. Gabon 8. Ghana
9. Kenya10. Liberia11. Mali12. Nigeria13. Tanzania14. Togo (past)15. Uganda 16. Zambia
ISNS 2016: Newborn Screening for SCD in Africa
… sickle-cell anemia contributes the equivalent of 5% of under 5 deaths on the African continent, more than 9% of such deaths in West Africa, and up to 16% of under-5 deaths in individual West African countries.
What happens to all those babies with SCD?
ISNS 2016: Newborn Screening for SCD in Africa
What happens to all those babies with SCD?
…..although current data are inadequate to support defınitive statements, they are consistent with an early-life mortality of 50%–90% among children born in Africa with SS disease.”
Grosse et al. Am J Prev Med 2011;41(6S4):S398 –S405
ISNS 2016: Newborn Screening for SCD in Africa
Newborn Screeningfor Sickle Cell Disease in Ghana
Kumasi-Tikrom Pilot Project
Sickle Cell Foundation of Ghana
ISNS 2016: Newborn Screening for SCD in Africa
GhanaPopulation: 26,327,649
Birth rate:31.09 births/1,000 pop. (2015 est.)
Annual births:820,000 (approx.)
KumasiPopulation: 2,070,000
2nd largest city in Ghana
Capital of Asante Region
Capital of “old” Asante Kingdom
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Sickle Cell Foundation of Ghana
Sickle Cell Foundation of Ghana
Project Funding1. U.S. Government: National Heart, Lung, and Blood
Institute (NHLBI) of National Institutes of Health (NIH), Comprehensive Sickle Cell Center Research Grant: 1993-1998; 1998-2003; and, 2003-2008 (PI: Ohene-Frempong
2. Government of Ghana: Ministry of Health and Ghana Health Service – Staff
3. Children’s Hospital of Philadelphia (CHOP) - Staff and donations
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Newborn Screening for SCD in Ghana
Sickle Cell Foundation of Ghana
Development of National Newborn Screening Programme (1/2)
1. Sickle Cell Foundation of Ghana, a non-profit NGO, formed in 2004 to:• lead advocacy for SCD programming and service;• administer newborn screening pilot project.
2. March 2008: US-NIH three 5-year funding cycles for the pilot project ended.
3. Screening continues with funding from Ministry of Health and National Health Insurance Authority, administered by Sickle Cell Foundation of Ghana (SCFG)
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Newborn Screening for SCD in Ghana
Sickle Cell Foundation of Ghana
Development of National Newborn Screening Programme (2/2)
4. Nov. 2010: National Programme of Newborn Screening for SCD (NNbSP-SCD) is launched by government• Technical Advisory Committee inaugurated• Steering Committee to be established to oversee
Programme• SCFG appoint Programme Managers and
Coordinating Agency
5. Nov 2011: Technical Advisory Committee presents Draft Policy and Detailed Plan for National Newborn Screening
6. 5-year national scale-up plan adopted
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Sickle Cell Foundation of Ghana
National Policy on Newborn Screening
As part of the Mission of the Ministry of Health to promote health and vitality for all people living in Ghana, reduce or prevent early mortality or morbidity from certain diseases detectable in newborn babies, and achieve the United Nations Millennium Development Goal (MDG) #4 - to reduce by two thirds, between 1990 and 2015, the mortality rate of children under five - the Ministry of Health has determined that all babies born in Ghana shall be offered screening for selected diseases and conditions after birth.
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Sickle Cell Foundation of Ghana
Issues Addressed:1.Programme Oversight2.Scientific Advisory3.Healthcare Provider Responsibilities4.Parental Education and Right of Refusal5.Human Samples Ownership6.Newborn Screening Data Ownership7.Confidentiality of Screening Data8.Healthcare Following Newborn Screening
National Policy on Newborn Screening
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Sickle Cell Foundation of Ghana
1. Donor / Research funding for pilot and feasibility studies2. National Health Insurance Authority
• Insurance Law: Healthcare for children < 5 yr FREE• Insufficient revenue from Value Added Tax
• Insufficient funding to meet primary obligations• Insufficient and irregular funding for NBS
3. Private Health Insurance - untested
4. Private corporate funding – untested; ?sustainability5. Personal ($5/baby) – political; under consideration
Barrier to Universal Newborn Screening: Sustainability
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Komfo Anokye Teaching Hospital, KumasiKumasi Centre for Sickle Cell Disease (KC-SCD)
• Established December 1992 with 10 patients - in preparation for Newborn Screening for SCD research project
• 1995: Newborn screening research project launched at KATH
• All babies started on penicillin, anti-malarial prophylaxis, folic acid. and comprehensive outpatient and inpatient clinical management.
• Ongoing family education with genetic counseling offered in clinic
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
KC-SCD: Clinic Enrollment of Newborn-Screened Patientsat End of 2015
Age Group (yrs)Active
PatientsSS SC
0-4 1,124 787 337
5-9 1,222 917 306
10-17 2,673 1,751 922
>18 1,394 767 627
TOTAL 6,413 4,221 2,192
• Possibly the largest number of newborn-screened cohort at a single clinical site.
• 4.5% babies died by age 5 yearsSickle Cell Foundation of Ghana
ISNS 2016: Newborn Screening for SCD in Africa
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project
Impact of Public Health Interventions on SCD Mortality
Piel et al. (2013) PLoS Med 10(7): e1001484. doi:10.1371/journal.pmed.1001484
1. Implementation in 2015 of prenatal diagnosis, penicillin prophylaxis, and anti-pneumococcal vaccination for children with SCD-
SS, can reduce mortality among children under-5 with SCD-SS, prolong the lives of 5,302,900 SCD-SS newborns with by 2050.
2. Large-scale universal screeningcould save the lives of up to 9,806,000 newborns with SCD-SS globally, 85% of whom will be born in sub-Saharan Africa
ISNS 2016: Newborn Screening for SCD in Africa
Sickle Cell Foundation of Ghana
1. Sickle cell disease is a major public health issue and among leading causes of under-5 mortality in Africa.
2. Newborn Screening for SCD is technically feasible and saves lives in Africa as it does elsewhere.
3. Newborn screening is a new public health intervention in Africa – new infrastructure, development of human and technical resources needed.
4. Funding and sustainability are major challenges
ISNS 2016: Newborn Screening for SCD in Africa
Conclusions
ISNS 2016: Newborn Screening for SCD in Africa
Tracking Babies with SCD in Kumasi
NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project