Control Strategies forControl Strategies for Hemoglobinopathies in India

Roshan B.ColahScientist F Dep t Director (SG)Scientist F- Deputy Director (SG),

National Institute of Immunohaematology,Parel, Mumbai

Population Statistics - Census of India – 2011p

Population - 1 21 billionPopulation - 1.21 billion(Represents 17.3% of the World’s population)Tribal population - 8.14%72 2% of the population live in 6 38 000 villages72.2% of the population live in 6,38,000 villages 27.8% of the population live in 5480 towns and citiesAge <25 years 50%Age - <25 years - 50%Literacy – 63.8% to 93.9% (Average- 74%)

Burden of Hemoglobinopathies

‐thalassemia carriers ‐ 1-17% thalassemia carriers 1 17% Hb E carriers - 2 –50%

Hb S i 0 35% Hb S carriers - 0 –35%Each Year 8,000 - 12,000 births with severethalassemiasthalassemias > 5000 births with sickle cell disease

Micromapping Studies on -Thalassemiain Western India

Individuals screened - 18,651Une en distrib tion of the freq encies of thalassemiaUneven distribution of the frequencies of -thalassemia Maharashtra - 1-6%Gujarat - 0-9.5%Expected annual births of homozyogtesp y gMaharashta - 588 (Maximum birth – Thane– 111)G j t 460 (M i bi thGujarat - 460 (Maximum births –

Junaghad – 104)

Colah et al. Br.J.Haematol, 2010; 149:739 -47

Management of children with -thalassemia major

• Estimated homozygotes - > 100,000

• Regular Transfusion - 10-15% of casesg& adequate iron chelationchelation

• Haemopoietic Stem Cell - Available at ~ 15 centresTransplantation Not affordable by most p y

families• Marrow Donor registries Being established• Marrow Donor registries - Being established

Verma et al Indian.J.Med.Res.2011; 134: 507-21

Establishment of Regional Centres for Screening – ICMR (2000 -2005)( )

Awareness  Screening 

Training for Carrier Detection

Counselling

Training for Carrier Detection

Challenges for Control of Hemoglobin DisordersChallenges for Control of Hemoglobin Disorders

Diverse population - Ethnicity, Culture, Religion, Literacy

Limited awareness - University students - 7 - 50%- Pregnant women - 0.2 -20%

MBBS d 19%- MBBS doctors - 19%Late registration in - 10-15% in the first trimester

l li iantenatal clinicsSocial stigmatization - Premarital screening generally not

t blacceptableInequality in - Urban v/s rural

il bilit favailability of services

Technology used for Screening gy g

-thalassemias RBC indices and HPLC analysis y Remote areas and resource poor settings –

NESTROFTNESTROFT

Sickle cell disorders Solubility TestSolubility Test Hb Electrophoresis or HPLC analysis

Borderline HbA2 Levels2

HbA 2 - 3.3 – 3.9% seen in 1 - 1.5% of -h l i hthalassemia heterozygotes

• Capsite +1 (AC), poly A (TC), -88 (CT)• Occasionally with IVS 1 – 5 (GC), CD 15 y ( ),

(GA), CD 30 (GA)• -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

-Thalassemia

Deletional thale et o a t aCaste Populations - 3.0 -23.0%Tribal Populations - 17 0 - 97 0%Tribal Populations 17.0 97.0%

HbH Disease is rare t ti i I di gene mutations in Indians

- 3.7, - 4.2, - - SA, - - SEA, Sallanches, poly A Indian

Shaji et al. Br.J.Haematol 2003;123:942-7Nadkarni et al. Genet. Test. 2008; 12:177-80Nadkarni et al Am.J. Clin. Pathol. 2010; 133:491-4

Screening and Management of Sickle Cell DisordersDisorders

National Rural Health Mission - Programmes in some states

Gujarat

I t t d i th i ti G t H lth S i Integrated in the existing Govt. Health Services 419 centres include - 333 Primary Health Centres

70 C it H lth C t- 70 Community Health Centres- 12 District General Hospitals

2 Go t Medical College- 2 Govt. Medical College- 2 NGO

Awareness and Education Programmes Awareness and Education Programmes Training for Medical Officers, Laboratory Technicians,

CounsellorsCounsellors Screening the tribal population

Sickle Cell Anemia Control Programme, NRHM, Gujarat, 2010

Centres for Prenatal Diagnosis in India

Chandigarh

g

Delhi

L k

Chandigarh

Atleast one Lucknow

Kolkata

one centre i h

Ahmedabad

Mumbai

in each state is

Hyderabadneeded

Vellore

Technology for Prenatal Diagnosis - Diagnostic approach

1st trimester CVS 2nd trimester Fetal blood1st trimester - CVS 2nd trimester – Fetal blood

HPLCRDB HPLC

ARMS

SequencingDNA analysis when required

Regional distribution of thalassemia mutationsRegional distribution of thalassemia mutations

Around 9,000 thal alleles characterized , 65 mutations

  th l t ti i t 7  –thal mutations are common in caste groups (>90% of alleles)

2 mutations common in tribals No of mutations - 5 to 22 in different statesNo. of mutations 5 to 22 in different states

Gujarat - CD 5 (-CT) - 3rd most commonGoa - IVS II – 837 (TG) - 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

Database of thalassemias andDatabase of thalassemias and hemoglobinopathies in India

ThalInd http://ccg.murdoch.edu.au/thalind

Sinha et al Hum.Mutat. 2011;32:887-93

Prenatal Diagnosis of Hemoglobinopathies atPrenatal Diagnosis of Hemoglobinopathies at NIIH (1986-2011)

1st Trimester - 1687N f P iNo.of Pregnancies

2529 2nd Trimester - 842

Prospective Diagnosis thalassemia - 7% of couples Sickle cell disorders - 33% of couples

Prenatal diagnosis & termination of affected pregnancies -A t bl b ll itiAcceptable by all communities

Colah et al Indian.J.Med.Res. 2011;134:552-60

Establishment of Regional Centres for Prenatal Diagnosis –ICMR (2008 -2011)( )

Training of Obstetricians & CMC,Ludhiana Sonologists

CVS NRS Medical

College,Kolkota

NIIH, Mumbai

Valsad Raktadan Kendra Valsad

Govt. Medical College Nagpur

Cordocentesis NIIH, Mumbai

Co-ord. Centre

College Nagpur

St.John Medical

College, Bangalore

Training in Molecular & Prenatal Diagnosis

g , g

CRDB

ARMS

VNTR analysis

Workshops in Medical Colleges(2010-2012)

Hands on training - Screening and molecular analysisin Hemoglobinopathiesin Hemoglobinopathies

Workshops held - 7

Medical Colleges covered - 41g

Pathologists/HematologistsPathologists/HematologistsScientists/ Lab Technologists trained - 109

Newborn Screening for Sickle CellNewborn Screening for Sickle Cell Disorders

Started in Maharashtra, Gujaratand Chattisgarhand Chattisgarh

Cohort of sickle homozygous babies (tribal and non - tribal) followed up

Greater awareness among these parents g p Few parents opted for prenatal diagnosis

i b t iin subsequent pregnancies

National Control Programme for HemoglobinopathiesHemoglobinopathies

Is being initiated by ICMR

Phase I – Delhi, Chandigarh and Punjab

Will eventually involve Central and State G & NGOGovernments & NGOs

Training and Quality Assurance will be included

AcknowledgementsAcknowledgements

Dr. K.Ghosh Dr D Mohanty Dr.D.Mohanty

Staff - Dept of Haematogenetics Staff - Collaborating Institutions Staff - Collaborating Institutions

Dr.Reena Das

THANK YOU