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National Institute of Immunohaematology, ICMR, Mumbai

Prevalence of sickle cell anemia in India:

• Madhya Pradesh

• Chhattisgarh

• Maharashtra

• Gujarat

• Kerala

• Orissa

• Jharkhand

• Andhra Pradesh

• Karnataka

• Tamil Nadu

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Activities of NIIH under THRF:

• Newborn screening (NBS) for Sickle Cell Disease and providing comprehensive care to understand the natural history of sickle cell disease in tribal populations in Madhya Pradesh and Gujarat

• Newborn Screening for Hemoglobinopathies and Red Cell Enzymopathies in Tripura

• Micro mapping of G6PD deficiency among the tribals of India and its importance for anti-malarial therapy

• Establishment of Prenatal Diagnosis of b Thalassemia Syndromes and Sickle Cell Disorders in Madhya Pradesh and Assam

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Newborn screening (NBS) for Sickle Cell Disease and providing

comprehensive care to understand the natural history of sickle cell disease in tribal populations in Madhya Pradesh and Gujarat

Participating Centers & Tribal groups

to be studied:

• NIRTH (Jabalpur): Gonds

• Valsad RaktdanKendra (Valsad) and Seva Rural Kendra (Bharuch): Dhodia, Patel, Gamits, KuknaWarli, Chaudhary

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New born screening results (Gujrat):

• Total number of New born Screened: 2827

–Normal: 2083 (73.6%)

–Sickle cell trait: 623 (22.0%)

–Sickle Cell Disease/ Sickle-b thalassemia: 58 (2.0%)

• Confirmation of the diagnosis was done by CRDB and ARMS (28/58 )

• Sickle cell anemia : 24• HbS- β- thalassemia: 4

IVS 1-5 (G→C) -3

CD 15 (G→A) -1

• 80/586 Sickle trait

Determination of -thalassemia

Phenotype Number of

Samples

Genotype

/ /-3.7 -3.7-/--3.7 -3.7-/--4.2

Normal 45 11 16 17 1

Sickle cell trait 37 4 6 27 -

b Thalassemia trait 1 - - 1 -

SCA 24 - 3 21 -

HbS-b Thalassemia 4 1 1 2 -

Total 111 16(14.4%) 26 (23.4%) 68 (61.2%) 1 (1%)

Determination of Xmn I Polymorphism

Phenotype Number of

Samples

Xmn I Polymorphism

+/+ +/- -/-

Normal 32 3 9 20

Sickle cell Trait 14 3 10 1

b-thalassemia trait 1 - - 1

SCA 24 24 - -

Sickle - b Thalassemia 4 - 4 -

Total 75 30 (40.0%) 23 (30.6%) 22 (29.3%)

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Total follow-up : 82 Cases

( 40 from earlier NBS and 42 present

NBS)

64 SCD & 18 S- β-thalassemia case

Clinical follow-up

Events Number ofaffected babies

%

Acute painful events 14 17.0

Severe anemia (Hb: ≤ 6.6 g/dl) and BT

13 15.9

Fever with cold andcough

20 24.4

Splenomegaly 7 8.5

Hospitalization 20 24.4

Death (Age: 4 yrs) on HU 1 1.6Clinical follow-up at Bharuch

Mobile Phone Distribution

• Total: 42 SCD families

• Received tremendous response

• Till now 24 calls were received

• Major complaints:

– Painful crises

– Fever with infection

– Breathlessness

– Swelling

• Necessary medical advice given for proper management.

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Awareness and Counseling among the

tribal communitieso Interaction with Anganwadi workers.

o Premarital counseling to individuals.

o Genetic counseling to the couples at risk.

o Total no. of couples counsel: 82

o PND opted: 23

o Affected Fetus : 6

o Preparation of the educational material

-

……

, .

Work done at NIRTH Jabalpur

• A total of 1444 pregnant womenhave been tested for varioushemoglobinopathies– 96 were Sickle cell carriers

– 7 were SCD

– 16 were β-thalassemia carriers

– 1 was HbE trait.

• Total 38 spouses were screened forcarrier/disease status and 13 highrisk couples have been found.

• Total 236 Cord blood samples havebeen collected and screened byHPLC.– 22 sickle cell carriers

– 2 Sickle Cell Disease

• SCD and sickle cell carriers arebeing followed every quarter

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Newborn Screening for Hemoglobinopathies and

Red Cell Enzymopathies in Tripura

• Total Newborns screened by HPLC – 1542

– Hb E Trait - 135 babies (8.7%),

– Hb E Homo/ Hb E thal. - 58 babies (3.7%)

– Suspected β-thal. trait – 49 babies (2.2%), Sickle

cell trait - 10 babies (0.7%)

• Confirmation of cases by Molecular analysis :

– HbE trait – 95/135 cases,

– HbE Homozygous – 21/55 cases

– β-thalassemia trait – 2/49 [IVS-15 (GC)]

– α-thalassemia – 25/52 (48.07%)

• G6PD deficiency – 13/1542 (0.8%)

• Training & Establishment of the laboratory for

molecular analysis for detection of

haemoglobinopathies and enzyme deficiencies at

Agartala Medical College

Micro mapping of G6PD deficiency

among the tribals of India and its

importance for anti-malarial therapy

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Micro mapping of G6PD deficiency among the tribals of

India and its importance for anti-malarial therapy

Principal Investigating Centre –NIIH, Mumbai

Co-investigating Centers

NIRTH - Jabalpur

RMRC - Belgaum

RMRC - Port Blair

RMRC - Dibrugarh

NIMR - Delhi (Jharkhand and Chattisgarh)

Number of Samples Screened at Valsad, Gujarat by NIIH Mumbai

TRIBES NO. TestedG6PD DEFICIENT

Male Female Total

Dhodia-patel 124 5 1 6 (4.8 %)

Dubala 55 1 1 2 (3.6%)

Koli-patel 102 1 1 2 (2.0%)

Warli 67 3 1 4 (6.0%)

Halpati 15 0 0 0 (0.0%)

Bhandari 13 0 0 0 (0.0%)

Others 32 1 0 1 (3.1%)

Total 408 11 (2.7%) 4 (1.0%) 15 (3.6%)

Screening for Mutational Analysis

CENTRES Total G6PD deficient tested

(G6PD activity IU/gmHb)

G6PD Orissa (131CG)

G6PD Mediterranean

(563 CT)

G6PD Kerala-

Kalyan

(949 GA

G6PD Coimbra

(592 CT)

G6PD*(551CT)

UC

NIIHGujarat

15 (0.01-2.07) 0 7 (46.6%) 0 6 (40.0%) 0 2 (13.3%)

NIMR Chattisgarh

27 (0.06-1.55) 18 (66.6%) 1 (3.7%) 0 4 (14.8%) 0 4 (14.8%)

NIRTH Jabalpur 47 (0.0-0.67) 33 (70.2%) 2 (4.2%) 0 0 3 (6.4%) 9 (19.4%)

RMRC

Belgaum

31 (0.08-1.80) 0 0 1 (3.2%) 0 0 30

(96.7%)

TOTAL 120 (0.0-2.07) 51 (42.5%) 10 (8.3%) 1 (0.8%) 10 (8.3%) 3 (2.5%) 45 (37.5%)

*: A new G6PD variant

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Establishment of Prenatal Diagnosis of b Thalassemia

Syndromes and Sickle Cell Disorders in Madhya

Pradesh and Assam

• National Institute of Immunohaematology, Mumbai– Meeting of the investigators

– Recruitment of staff

– Hands on training for newly appointed staff of NIIH, Mumbai and NIRTH Jabalpur : HPLC, CVS cleaning, CRDB, ARMS.

– Quality control programme

– Preparation of Educational material : Booklets, Posters and Handouts.

Establishment of Prenatal Diagnosis of b Thalassemia

Syndromes and Sickle Cell Disorders in Madhya

Pradesh and Assam

• National Institute for Research in Tribal Health, Jabalpur

Recruitment of staff

A total of 24 high risk couples have been identified

Three high risk couples were referred to NIIH, Mumbai for PND

Efforts are also being made to obtain license from the state health

authorities for initiating CVS sampling through the partner NSCB medical

college

• Regional Medical research Centre, Dibrugarh

Recruitment of staff

Necessary arrangement has been made with the collaborators of Assam

Medical College & Hospital

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SICKLE CELL AND MALARIA TRAINING CARRIED OUT IN

COLLABORATION WITH MINISTRY OF TRIBAL AFFAIRS (MOTA),

NEW DELHI

• Odisha

• West Bengal

• Assam

• Arunachal Pradesh

• Mizoram

• Manipur

• Tripura

• Jharkhand

• Madhya Pradesh

• Tamil Nadu

• Chhattisgarh

• Uttar Pradesh

Resourced by NIRTH

• Gujarat

• Kerala

• Karnataka

• Rajasthan

• Maharashtra

Resourced by NIIH

Master training

• Odisha

•West Bengal

•Tripura

•Tamil Nadu

•Himachal Pradesh

Master training

• Rajasthan

•Maharshtra

Latest update on Screening of Sickle Cell in States

Name of the State Remarks

Arunachal PradeshThe screening initiated.

Chhattisgarh The screening in progress since August 2015

Himachal PradeshThe screening initiated in March, 2016

Jharkhand The screening in progress.

Madhya PradeshThe screening in progress since April 2015

Maharashtra NIIH. Screening in Progress

Manipur Screening Initiated

Rajasthan Screening in progress. NIIH/DMRC Screening Since October 2015

Tamil NaduFunds received by state Govt in the last week of March, 2016 and not transferred to TRI, Ooty.

Telangana The screening process is still on (NIIH)

Tripura Screening ongoing since August 2015 (78000 screened; 69 Positive)

Uttar Pradesh Screening Initiated in March 2016

West Bengal Screening under progress since November 2015

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Desert Medicine Research Centre, Jodhpur

• In partnership with State Medical and Health Services, Govt. ofRajasthan, the Centre has initiated a study entitled “Assessment oftribal students under the Tribal Sub-Plan Districts of Rajasthan forSickle Cell Disease (SCD), Sickle Cell Trait (SCT) and development ofappropriate intervention model” funded by the Tribal AreaDevelopment Department, Govt. of Rajasthan.

• A collaborative study between DMRC, Jodhpur; Govt. MedicalCollege, Kota and State Medical and Health Services, Govt. ofRajasthan is undergoing entitled “Improving Health and NutritionalStatus of Sahariya tribal population of Rajasthan by intersectoralconvergence as a sustainable model of intervention.

Assessment of tribal students under the Tribal Sub-Plan Districts of Rajasthanfor Sickle Cell Disease (SCD), Sickle Cell Trait (SCT) and development ofappropriate intervention model.

• Objectives:• To carry out screening of tribal students of tribal sub-plan districts of

Rajasthan for Sickle Cell Disease (SCD) & Sickle Cell Trait (SCT) andnecessary genetic counselling.

Coverage Target populationResidentHostel

17,474 Students of Ashram hostels, Eklabya Model Public School,Model Public Residential School, Khel Hostel and AbasiyaVidyalaya located in five district, (Tribal Sub-Plan Area) ofRajasthan.

Day CareCentres

30,000 Students of Maa Baadi Day Care Centres & Maa BaadiKendras located in five districts (Tribal Sub-Plan Area) ofRajasthan.

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• The study was undertaken as a pilot mode in a TribalGirls Hostel, Udaipur in October 2015

• A total of 133 students were screened for the sicklecell disease and their Hb level was estimated. Theresults given below

Subject

Group

Normal

(> 12 g/dl)

n (%)

Mild

Anemia

(11-11.9

g/dl)

n (%)

Moderate

Anemia

(8-

10.9g/dl)

n (%)

Severe

Anemia

(< 8g/dl)

n (%)

Sickle-cell

Adolescent

girls

(n = 133)

52 (39) 47 (35) 32 (24) 2 (2) Nil

Improving Health and Nutritional Status of Sahariya tribal population of Rajasthan by intersectoral convergence as a sustainable model of intervention

• Work done so far:

• The screening of the Sahariya population for the Sicklec Cell Disease is undergoing in the BaranDistrict of Rajasthan.

• Screening of the 535 subjects were conducted forthe sickle cell disease and their Hb level wasestimated. The results given below

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Results of Sickle Cell prevalence and Anemia

Benefici

aries

Normal

(> 12 g/dl)

n (%)

Mild

Anemia

(11-11.9

g/dl)

n (%)

Moderate

Anemia

(8-10.9g/dl)

n (%)

Severe

Anemia

(< 8g/dl)

n (%)

Sickle-cell

Women

(n= 393)

42 (11) 43 (11) 196 (49) 112 (29) Nil

Adolesce

nt girls

(n = 142)

23 (16) 24 (17) 62 (43) 34 (24) Nil

Satellite Centre for

Hemoglobinopathies at

Chandrapur

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Four acre of land has been accrued at Chandrapur

• Renovation of TB Hospital

• Appointment of the Staff

• Procurement of furniture

• Procurement of Chemicals and

Reagents

• Procurement of small equipments

• Boundary wall of the accrued land

Progress of the center

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Establishment of

Laboratories

Establishment of

Laboratories

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• Identification of Cases through Community

Screening

• Antenatal Screening Programme

• New born Screening Programme

• Role of Genetic Modifiers for Disease Severity

Plan of Work

Work Done in the Last three Months

• Community Screening– Total Screened : 300

– Sickle Cell Carrier: 45 (15.0%)

• Identification of Cases through NRHM & Govt. Hospital– Sickle Cell Disease: 80

– Sickle Beta thalassemia: 10

– Beta Thalassemia Major: 20

• Antenatal Screening– Total Screened: 200

– Sickle Cell Carrier: 20

– High risk Couples identified: 5

– Total No. of Couples counseled: 5

– Agreed for PND: 2

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Challenges in control of sickle cell anemia:

• Comprehensive care of sickle cell anemia patients

– Access to quality care facilities

– Implementation of awareness programs

– Screening and genetic counseling in antenatal clinics

– Easy access to antenatal diagnosis

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Sickle cell anemia:

• 50% of total AS and SS neonates are born in only 3 countries: Nigeria, India and DR Congo

• Estimate for number of neonates with SS born in India per year is 42,016 which is 88% of the total homozygous cases in Asia

• However the prevalence is varies significantly in different populations (0-35%)

• Largely restricted to tribal populations and scheduled casts and other backward communities

Multicentric Studies on Haemoglobinopathies

G6PD Deficiency – 8 States

NIRTH, NIIH, NIMR, RMRC Belgaum, Portblair,

Dibrugarh; RIMS Ranchi; Govt. Medical College,

Jagdalpur.

Sickle Cell : Prenatal Screening – 4 States

NIRTH, NIIH, RMRC Dibrugarh & Portblair

Newborn Screening for Sickle Cell Disease –

3 States

NIRTH, NIIH & Valsad Raktdan Kendra