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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

Disclosure of Conflict

ISNS 2016: Newborn Screening for SCD in Africa

No personal conflict

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)


*80 % born in low and middle income countries

What is sickle cell disease?


Wright-Giemsa stained blood smear

Sickle Cells


A. Normal red cell B. Sickled red cell

Scanning Electron Micrographs




• 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.


SCD: Dactylitis (“hand-foot syndrome”)


Pain!……. the hallmark of sickle cell disease

“10” redefinedHertz Nazaire


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.


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

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


Why screen newborns for

sickle cell disease?


Causes of Death in SCD-SS (0-10 yr)

(Gill FM, et al, CSSCD: 1995)Overall incidence: 1.1/100 person-yrs


Bacteremia in SCD-SS Disease, CSSCD

Infection in SCD


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


Newborn Screening for SCD

Improved Survival in Children with SCD

Effect of Newborn Screening for SCD


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


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


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


… 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?


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


Newborn Screeningfor Sickle Cell Disease in Ghana

Kumasi-Tikrom Pilot Project

Sickle Cell Foundation of Ghana


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


NBS for SCD in Ghana: Kumasi-Tikrom Pilot Project



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



Newborn Screening for SCD in 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)





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




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.




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




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



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



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



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



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


Conclusions


Tracking Babies with SCD in Kumasi




Follow up of Children with SCD in Tikrom



Documents

Newborn Screening for Sickle Cell Disease in Africa ...s05.qind.nl/userfiles/812/File/I18 Ohene-Frempong-ISNS-2016-13-Sep... · Newborn Screening for Sickle Cell Disease in Africa: