Current Situation in Control Strategies and Health Systems in Asia - India by Roshan B.Colah, Scientist F- Deputy Director (SG), National Institute of Immunohaematology, Parel, Mumbai

1. Control Strategies for
Hemoglobinopathies in India
Roshan B.Colah
Scientist F- Dep t Director (SG),
F Deputy (SG)
National Institute of Immunohaematology,
Parel, Mumbai

2. Population Statistics - Census of India – 2011
p
Population - 1 21 billion
1.21
(Represents 17.3% of the World’s population)
Tribal population - 8.14%
72.2%
72 2% of the population live in 6,38,000 villages
6 38 000
27.8% of the population live in 5480 towns
and cities
Age - <25 years - 50%
Literacy – 63.8% to 93.9% (Average- 74%)

4. Burden of Hemoglobinopathies
 ‐thalassemia carriers ‐ 1-17%
 thalassemia 1 17%
 Hb E carriers - 2 –50%
 Hb S carriers - 0 –35%
i 35%
Each Year
8,000 - 12,000 births with severe
thalassemias
> 5000 births with sickle cell disease

5. Micromapping Studies on -Thalassemia
in Western India
Individuals screened - 18,651
Une en distribution of the freq encies of  thalassemia
Uneven distrib tion frequencies -thalassemia
Maharashtra - 1-6%
Gujarat - 0-9.5%
Expected annual births of homozyogtes
p y g
Maharashta - 588 (Maximum birth – Thane– 111)
Gujarat
G j t - 460 (Maximum births –
(M i bi th
Junaghad – 104)
Colah et al. Br.J.Haematol, 2010; 149:739 -47

6. Management of children with -thalassemia major
• Estimated homozygotes - > 100,000
• Regular Transfusion
g - 10-15% of cases
& adequate iron
chelation
• Haemopoietic Stem Cell - Available at ~ 15 centres
p
Transplantation Not affordable by most
y
families
• Marrow Donor registries - Being established
Verma et al Indian.J.Med.Res.2011; 134: 507-21

7. Establishment of Regional Centres for Screening – ICMR
(
(2000 -2005)
)
Awareness Screening
Counselling
Training for Carrier Detection
Training for Carrier Detection

8. Challenges for Control of Hemoglobin Disorders
Diverse population - Ethnicity, Culture,
Religion, Literacy
Limited awareness - University students - 7 - 50%
- Pregnant women - 0.2 -20%
- MBBS doctors - 19%
d
Late registration in - 10-15% in the first trimester
antenatal clinics
l li i
Social stigmatization - Premarital screening generally not
acceptable
t bl
Inequality in - Urban v/s rural
availability of
il bilit f
services

9. Technology used for Screening
gy g
-thalassemias
 RBC indices and HPLC analysis
y
 Remote areas and resource poor settings –
NESTROFT
Sickle cell disorders
 Solubility Test
 Hb Electrophoresis or HPLC analysis

10. Borderline HbA2 Levels
HbA 2 - 3.3 – 3.9% seen in 1 - 1.5% of -
thalassemia h
h l i heterozygotes
• Capsite +1 (AC), poly A (TC), -88 (CT)
• Occasionally with IVS 1 – 5 (GC), CD 15
y ( ),
(GA), CD 30 (GA)
• -thalassemia heterozygotes with  gene
 yg g
mutations
• - thalassemia heterozygotes with  gene
 yg g
triplication
Garewal et al Eur.J.Haematol. 2007; 79:417-21
Colaco et al Indian.J.Haemtol. & Blood. Transf. 2011; 27:242

11. -Thalassemia
 Deletional  thal
e et o a t a
Caste Populations - 3.0 -23.0%
Tribal Populations - 17.0 97.0%
17 0 - 97 0%
 HbH Disease is rare
 gene mutations in Indians
t ti i I di
- 3.7, - 4.2, - - SA, - - SEA,  Sallanches,  poly A Indian
Shaji et al. Br.J.Haematol 2003;123:942-7
Nadkarni et al. Genet. Test. 2008; 12:177-80
Nadkarni et al Am.J. Clin. Pathol. 2010; 133:491-4

12. Screening and Management of Sickle Cell
Disorders
 National Rural Health Mission - Programmes in some states
Gujarat
 I t
Integrated i th existing Govt. Health Services
t d in the i ti G t H lth S i
419 centres include - 333 Primary Health Centres
- 70 C
Community H lth C t
it Health Centres
- 12 District General Hospitals
- 2 Go t Medical College
Govt.
- 2 NGO
 Awareness and Education Programmes
 Training for Medical Officers, Laboratory Technicians,
Counsellors
 Screening the tribal population
Sickle Cell Anemia Control Programme, NRHM, Gujarat, 2010

13. Centres for Prenatal
Diagnosis in India
g
Chandigarh
Atleast Delhi
one Lucknow
L k
centre Ahmedabad Kolkata
in
i each h
state is Mumbai
needed Hyderabad
Vellore

14. Technology for Prenatal Diagnosis - Diagnostic approach
1st trimester - CVS 2nd trimester – Fetal blood
HPLC
RDB
ARMS
DNA analysis when
Sequencing required

15. Regional distribution of  thalassemia mutations
 Around 9,000  thal alleles characterized
,
 65 mutations
 7  –thal mutations are common in caste groups
 th l t ti i t
(>90% of alleles)
 2 mutations common in tribals
 No of mutations - 5 to 22 in different states
No.
Gujarat - CD 5 (-CT) - 3rd most common
Goa - IVS II – 837 (TG) - most common
Garewal et al . Br.J.Haematol. 1994; 86:372-6 Verma et al Hum. Genet. 1997; 100: 109-13
Edison et al. Clin. Genet. 2008; 73: 331-7 Colah et al Blood Cell Mol. Dis. 2009; 42: 241-6

16. Database of  thalassemias and
hemoglobinopathies in India
ThalInd
http://ccg.murdoch.edu.au/thalind
Sinha et al Hum.Mutat. 2011;32:887-93

17. Prenatal Diagnosis of Hemoglobinopathies at
NIIH (1986-2011)
1st Trimester - 1687
No.of Pregnancies
N fP i
2529 2nd Trimester - 842
Prospective Diagnosis
 thalassemia - 7% of couples
 Sickle cell disorders - 33% of couples
Prenatal diagnosis & termination of affected pregnancies -
Acceptable b all communities
A t bl by ll iti
Colah et al Indian.J.Med.Res. 2011;134:552-60

18. Establishment of Regional Centres for Prenatal Diagnosis –
ICMR (2008 -2011)
( )
Training of Obstetricians &
CMC,Ludhiana
Sonologists
CVS
Valsad Raktadan
Kendra Valsad
NRS Medical
College,Kolkota Cordocentesis
Govt. Medical
NIIH, Mumbai College Nagpur
Co-ord. Centre
Training in Molecular & Prenatal
St.John Medical
College, Bangalore
g , g
Diagnosis
CRDB
ARMS
VNTR analysis

19. Workshops in Medical Colleges
(2010-2012)
Hands on training - Screening and molecular analysis
in Hemoglobinopathies
Workshops held - 7
Medical Colleges covered
g - 41
Pathologists/Hematologists
Scientists/ Lab Technologists trained - 109

20. Newborn Screening for Sickle Cell
Disorders
 Started in Maharashtra, Gujarat
and Chattisgarh
 Cohort of sickle homozygous babies
(tribal and non - tribal) followed up
 Greater awareness among these p
g parents
 Few parents opted for prenatal diagnosis
in b
i subsequent pregnancies
t i

21. National Control Programme for
Hemoglobinopathies
 Is being initiated by ICMR
 Phase I – Delhi, Chandigarh and Punjab
 Will eventually involve Central and State
Governments & NGOs
G NGO
 Training and Quality Assurance will be
included

22. Acknowledgements
 Dr. K.Ghosh
 Dr D Mohanty
Dr.D.Mohanty
 Staff - Dept of Haematogenetics
 Staff - Collaborating Institutions
 Dr.Reena Das

23. THANK YOU