Sickle-cell disease

Institut national de la santé et de la recherche médicale

Sickle Cell Disease International collaboration and global issues Jacques Elion, MD, PhD National Reference Centers for Sickle Cell Disease Department of Medical Genetics Robert Debré University Hospital, 75019 Paris, France Inserm UMR 665 National Institute for Blood Transfusion, 75015 Paris Guadeloupe University Hospital, 97139 Les Abymes (French West Indies)

La Havana 20-24 May 2013

Independent origins of SCD in Africa and India

Map is from Piel FB et al: Nature Communications, Nov 2010

Spread by the slave trade

Norvège

Finlande

Suède Irlande

Danemark

Royaume Uni

France

Pays-Bas Belgique Luxembourg Allemagne

Italie Espagne Portugal Grèce

βS …or modern economical migrations

The burden of the haemoglobinopathies It is estimated that in excess of 300 000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries. Major hemoglobin disorder

No. of annual births

β thalassaemia major

22 989

HbE β thalassaemia

19 128

HbH disease

9 568

Hb Bart hydrops (α°)

5 183

SS disease

217 331

S β thalassaemia

11 074

SC disease

54 736

Sickle cell anaemia is by far the commonest and data suggests that close to 180 000 babies are born each year in sub-Saharan Africa with this condition Weatherall DJ. Blood. 2010

Affected newborns in subsaharan Africa

Nigeria

Modell, 2006

Sickle Cell Disease in India Burden of Disease Estimates births/year: AS: 2,434,170 SCD-SS 121,375 (Mohanty, ’02) (0-18%)

(0-18% (0-1%)

(0-31%)

(0-30%)

(0-2%)

(0-35%) (0-12%) (0-33%) (0-34%)

25-40% carriers (0-23%)

(0-31%) (0-20%)

SCD is recognized as a global public health issue • African Union: Assembly decision/AU/ Dec. 81 July 2005 • UNESCO General Assembly September 2005 • WHO resolutions: WHA59.20 and EB 118 May 2006 • UN General Assembly resolution: A/63/237

December 2008

• WHO-AFRO resolution: August 2010 Still many issuesAFR/RC60/8 remain unanswered Sickle-cell disease: a strategy for the WHO African Region

Epidemiological data must be interpreted with extreme caution - based mainly on studies that were carried out before 1980 (in Africa) - obtained from a very limited number of centers in each of the countries - even in many richer countries, data of this kind are scarce Thus, there is an urgent need of sound epidemiological data to estimate the health burden that will be encountered, particularly by the poorer countries as the haemoglobin disorders become even more frequent in the future. Weatherall DJ. Blood. 2010

unresolved issue 1

The epidemiologic transition Because of: - improved nutrition - better control of infectious disease …childhood mortality rates are decreasing Under these circumstances, the prevalence of genetic disorders like haemoglobinopathies tends to increase Furthermore, in many cases this affects countries with the highest rate of increase of their population. But census data are uncertain unresolved issue 2

SCD is apparently a simple disease - a single gene - a single mutation - a “simple” basic pathophysiological scheme still it is highly variable in its clinical presentation - cell adhesion - inflammation - endothelial damage - altered hemorheology - NO bioavailability

unresolved issue 3 Steinberg, N Engl J Med 1999

What is the problem? - basic research has been done in the North, mostly in the USA - all the tools are there (pharmalogical labs, facilities for GWAS studies…) but - we lack epidemiological data - we know almost nothing about the natural history of SCD in its natural environment

Worldwide disparity of resources approx. - 100,000 SCD patients in the US - 50,000 SCD patients in Europe

Hundreds of thousands SCD patients in sub-Saharan Africa AND India Brazil is by far the country with the largest number of patients in the Americas, just followed by the Carribean countries

Worldwide disparity of resources approx. - 100,000 SCD patients in the US - 50,000 SCD patients in Europe

Hundreds SCD patients in sub-Saharan Global issueof→thousands clear necessity of coordinated efforts Africa AND India - South-South sustainable collaboration - North-South equitable sustainable collaboration Brazil is by far the country & with the largest number of patients in - triangular the Americas,partnerships just followed by the Carribean countries regional and international (global) networks

It is clear that research, training of doctors and health workers and education can be the driving force to improve clinical care globally to the mutual benefit of both low- or middleincome countries and high-income countries and for the good of the patients.

International collaboration is crucial

International collaboration Examples of fruitful collaborative networks - France – French-speaking African countries - UK - Tanzania - Portugal – Angola - Holland – Curaçao - USA – Ghana - Brazil – Ghana, Senegal, Benin, Angola

Within this frame, regional networks and international coordination are pivotal to promote: - research - training and education - patients follow-up and management

Comparative cohort studies are badly needed Results of projects such as the Jamaican Cohort Study or the USA Cooperative Study of Sickle Cell Disease are clear indications that such initiatives should be pursued in a comparative manner. Definition of the phenotype is crucial. Given the level of complexity of SCD it is is difficult to achieve an agreed classification of the different degrees of severity. It is vital to attempt to produce a workable description of severity as a prelude to the potential international collaborations and to normalise clinical and biological data collection. Weatherall et al. Blood. 2005

Examples of successful regional networks

Africa (1)

REDAC The Central African SCD network - Cameroon - DRC - Congo - CAR - Gabon - Tanzania - South Sudan

Angola Ouganda Zambia Kenya Burundi Ruanda


Africa (2) Research Networks

Cohort of 5.000 patients

CADRE study SCD cardiovascular aspects Brigitte Ranque, Xavier Jouven et al Laboratoire d’Excellence GR-Ex Coordonnation: Olivier Hermine


SickleCHARTA PI: Julie Makani Tanzania Establish a network of Excellence SCD Centres in Africa - Epidemiological genetics GWAS studies

- Healthcare - Training

Sanger Institute

Cohort: 10.000 SCD patients

NIH


Caribbean Network

CAribbean network of REsearchers on

President : MD Hardy-Dessources

11 Caribbean countries Sickle cell disease and Thalassemia

- Newborn screening - Follow-up - Education - Research

Relationship between Acute Chest Syndrome and the sympathovagal balance in adults with hemoglobin SS disease; a case control study Knight-Madden JM, Connes P, Bowers A, Nebor D, HardyDessources MD, Romana M, Reid H, Pichon AP, Barthélémy JC, Cumming VB, Elion J, Reid M. 2012, sous presse.

The Global SCD Network Medical Director: Isaac Odame SickKids Hospital, Toronto

• Mission

International Advisory Board: Jacques Elion, Chairman

– Furthering research and advancing clinical care globally

• Goals – Facilitate North-South, South-South and triangular partnerships • • • •

Research Training Education Clinical programs

Foundational and Transformative GSCDN IMMEDIATE PRIORITIES

SHORT /MEDIUM TERM PRIORITIES

LONG TERM PRIORITIES

HIGH

Foundational

Transformative

Visionary

Standard SC Centre Model Rollouts 1 SCD Model Centre Implement Programs In 3 or 4 LICs

Published data of SCD related mortality

SCD Leader, WHO Partner , Continued SC Centre Expansion

SCD Centre Planning Establish Int’l Advisory Council

Foster Partnerships; start with CDC, UNESCO

GSCDN Conference at CDC NINGSite GSCDN Website

LOW

HIGH

Level of Effort to Implement * Red line indicates maturity curve

GSCDN Website www.globalsicklecelldisease.org

Interactive Treatment Centres Map

http://www.globalsicklecelldisease.org/

GSCDN ‘Ning’ Online Community http://globalscd.ning.com




HIGH

Foundational

Transformative

Visionary




SCD Centre Planning Establish Int’l Advisory Council

Foster Partnerships; start with CDC, UNESCO


LOW

HIGH


Sickle cell disease in Africa: a neglected cause of early childhood mortality. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Am J Prev Med. 2011




HIGH

Foundational

Transformative

Visionary




SCD Centre Planning Foster Partnerships; start with CDC, UNESCO

Establish Int’l Advisory Council


LOW

HIGH


Sickle cell disease in Africa: a neglected cause of early childhood mortality. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Am J Prev Med. 2011

GSCDN and the regional SCD Networks The importance of local management in reinforcing the whole

SI C KL E

L A B O GL

CE LL

CAREST

DIS E

REDAC

AS E

W T E N

K R O

s e t r e r u e f g s n a o r m t s s s e o t t b r n l o l f i Ju s w u e l p w r s e n h o t r e e g s s To u o n e l b ô f m i l e ! s p s é k En k r o u w o t n e N m n D a C s S n n A i o J / e z i n a g r O