Haemoglobinopathies in Africa - Léon Tshilolo

HEMOGLOBINOPTAHIES IN AFRICA

Léon Tshilolo, MD, PhDUNESCO HVP meeting

30-31 May 2016

WHO recommended the implementation of national SCA programs in Sub-Saharan Africa region with a focus on widespread awareness-raising, early identification, early access to adequate preventative care, and training of medical professionals.

Main focus of SCD

Geographical distribution and haplotypes

Coïncidence with malaria map

4 main focus(haplotypes)• Bénin• Sénégalais•Cameroun• Bantu (CAR)

Genetic diversity

A map of African language family distributions and hypothesized migration events within and out of Africa. (Campbell, Tishkoff 2009)

Prevalence of Hemoglobinopathies in Africa

0

5

10

15

20

25

30

35

40

Burkina Fas

o Benin

Nigeria

Guine

a

S Le

one M

ali

Ango

la

Con

go

D R

Con

go

Gab

on

Gha

na

Niger

C d'Iv

oire

Equ Guine

a

Libe

ria Togo

Gam

bia

G-B

issa

u

S T & Prin

cipe

Sene

gal

Uga

nda

Cam

eroo

n

Tanz

ania

Zambia

C Afr Rep

Mad

agas

car

Burund

i

Cha

d

Moz

ambiqu

e

Malaw

i

Rwan

da

Keny

a

Cap

e Ve

rde

Mau

ritius

Mau

retania

Zimba

bwe

Com

oros

May

otte

Reu

nion

Alge

ria

Seyc

helles

S Afric

a

Carriers, %

of the

pop

ulation

a0 thal

AE

Beta thal

AS

AC

Environmental and genetics factors• Tropical climate:

– malaria endemic, – High prevalence of HIV (4-15%)

• Socio economic conditions:– Poverty– independence since 50 years– Very rare Comprehensive SCA programs

• Homogenous population in DRC– Bantu haplotype: > 80%– Alpha-thal deletion: 10-50%– G6PD deficiency: 20-40%

EXPRESSION OF SCD in CENTRAL AFRICA

High morbidity and mortality

• Frequent VOC and high frequency of blood transfusion n (0.4U/yr)

• Severe complications

Early manifestationsHand Foot SyndromeAcute anaemiaSplenic SequestrationSepsis and pneumoniae (fever)

Septicemiae and meningitis•High mortality in very young children < 2 yrs•Str. Pneumoniae, Haemophilus Infl.

Respiratory infections: pneumoniae

Sreptocccus pneumoniae

Bone infectionsSalmonella sp : mainly in SCA patients

fistula

infections of international interestTuberculosis

• lung• bones

Malaria• Anemiae• CVO• Malnutrition• High risk Pregnancy• Mortality

Hepato-splenomegaly

• Large spleen• Persistent after 5yrs of age• Related to malaria?• Alpha –thalassemia

• Hepatomegaly• Viral infectious?• Iron hyperloading?

NTE manifestations

Nose bleeding

Hypertrophic tonsillitis Upper air obstruction

Dental abnomarlities

EARLY DIAGNOSIS

• Newborns and Children < 5yrs

• Samples : Dry blood and/or EDTA (Cord blood)

• IEF or HPLC: basic system (fisrt line method)

• Solubility test (Itano) in children > 1yr

• Capillary Electrophoresis (CE) : confirmation test

• Rapid diagnostic tests

Danielle Lena, PharmD

Hôpital d'enfants de la Timone, Marseille, France Monacord program

Dépistage et prise en charge des enfants atteints de syndrome drépanocytaire majeur dans les pays en développementScreening and management of children with sickle cell syndromes in developing countries

Kampala, UgandaMay 25-27, 2015

80’s Justification of newborn screening

Effective intervention in children with sickle cell disease provides a major impetus for neonatal screening

Prophylactic penicillin therapy has been found to significantly reduce the morbidity and mortality of patients with pneumococcal sepsis 1986

Antipneumococcal/haemophilus immunization

Antimalarial prophylaxis

Reliable, simple, and cost-effective techniques for mass screening of neonates are available.

Conditions of newborn screening

To be effective, neonatal screening must be part of a comprehensive program for the care of sickle cell patients and their families, including:

- a network of providers who ensure optimal medical care

- psychosocial support and genetic counseling.

Such follow-up capabilities should be in place before or coincidentally with screening implementation

Benin

1993: Pioneer programs in Africa

Ghana

2007: Pilot study Léna et al.

5 Countries - Morocco - Tunisia - Senegal - Mali - R Congo

Feasability

Enrolment in a follow-upProgram

5,000 samples

Results Léna et al. 2007

SS

SS

Results Léna et al. 2007

SS

SS

SS + SCSbThalSS + SbThal

Results Léna et al. 2007

SS

SS

SS + SCSbThalSS + SbThal

SOArab

Results Léna et al. 2007

SS

SS

SS + SCSbThalSS + SbThal

SOArab

Only 50% of the affected could be retrieved and enrolled in a follow-up program

30 questionnaires 19 answers

2016: What is the status today?

Most often 1 center or more 2-4 in capital cityPointe Noire

In some countries centersin different cities 2 in Angolato 11 in Nigeria

Newborn screening

.. .. . .. ... . .

Multiple centers

Angola 2Benin 1 + 2Mali 1 + 2Nigeria 8DRC: 4

Specialized centers

56% to 100% of the affected children have been enrolled in a follow-up program

Preventive measures

Peni VFolic ac.Immunization PneumoOpioids

TCD

93%100%100%80%

80%

Conclusions of the survey

impressive increase in the number of screening programs and specialized centers

BUT

most are pilot projects

no universal screening

difficulties in retrieving the affected children

Limited management of SCA patients

Exemple of Newborn screening in DRC

HET-EROZY-

GOTE AS; 16.8% HO-

MOZY-GOTE S;

1,7%

NORMAL A; 81,5% 81,5% AA, 16,8% AS, and 1.7% SS. No βSthal have been found but only few Bart’s Hb suggesting the co-existence of α-thal deletion

Clinical manifestations in Sickle cell trait patients: interest for genetic studies

• Splenic infarction at high altitudes

• Essential hematuria

• Loss of renal concentration ability

• Sudden death after extreme exertion

• Thromboembolism disease

Impact of genetic and environmentfactors

• Genetic factors determining clinical and laboratory heterogeneity in Sickle Cell Disease.

• The focus will be on clinical-laboratory outcomes (anaemia, haemolysis, foetal haemoglobin, infections, and neurological events)

• Pharmacogenomic response to treatment (hydroxyurea and antibiotics).

What we need

SCD

Healthcare

Training

Advocacy

Research

Genomic Research

Health benefits

GenotypingLaboratory capacity

Phenotyping Haemolysis, HbF, infections,

inflammation, Stroke

Statistical and Epidemiological Analysis

Bioinformatics Clinical Studies

The need of a Regional Collaboration and North-South parternership

Thank you/ Merci

Dank U/Aksanti