Prevention of hemoglobinopathies.pptx……..

how to out come anemia

1. Prevention of Hemoglobinopathies Dr S.SHANTHI - Expert Advisor – NHM ( Blood & Blood Disorders) NHM – online workshop 3.4.2023

2. World wide 240 million carriers of beta thalassemia Mean prevalence in India-3.3% Every year approximately 1,00,000 children are born of whom 10,000 are born in India. Total cost of treating a child in India- 2,10,000INR/child/year Need for prevention

3. In Cyprus the prevalence of affected births was reduced from 1:138 to 1:1000. Successful implementation of the prevention and control programme has brought down the birth rate to almost zero. In Sardinia , Italy voluntary carrier screening programme has reduced incidence from 1:250 to 1:4000. In Montreal, Canada high school voluntary screening programme has led to 95% decrease in incidence of beta thalessemia . Success stories

4. Different countries have different target groups General population screening at school age: Thailand Premarital screening in middle east countries like North Cyprus where abortion is not generally accepted. Screening of couples at marriage or in early pregnancy- Sardinia, Italy . Cascade screening in Pakistan . Global Screening Efforts

5. Carrier detection Genetic counseling Prenatal diagnosis Major strategies

6. For early disease : in newborn-for thal major and SCA in childhood from 6 months to 6 years with severe anemia For carriers: adolescents premarital preconception antenatal and cascade screening. Screening

7. Newborn Screening: Suspected cases of thalassemia major due to beta 0/beta0 genotype manifesting as complete absence of HbA in the Hb pattern, for confirmation on follow up at 12 months of age. It is more useful for identification of sickle cell anemia than thalassemia . Screening for disease

8. Screening for disease Childhood (6 months – 6 years): Universal screening of all children with severe anemia( H b <7gm/dl ) Also identifies thalassemia intermedia Cost effective Comprise pre school age group and are reached through anganwadis .

9. Adolescence: Universal screening of all adolescents . High acceptance rate with retention of information among students. Helps in removing stigma due to acceptability to all students. Has been implemented as a part of pilot project on birth defects in the govt. schools of Uttrakhand . Screening for trait

10. Pre-marital screening: Screening offered to those individuals who seek it A carrier is left with two options 1. Not going ahead with marriage. 2. Prenatal diagnosis later in each of the pregnancies if the spouse is also a carrier. Screening for trait

11. Pre conception screening: OPTIONS: Prenatal diagnosis with termination of pregnancy. Adopting a child better than having their own child withstanding 25% risk factor. Couple can also seek pre implantation genetic diagnosis . Screening for trait

12. Antenatal screening Universal screening should be offered to all pregnant women during the first trimester at all levels. States providing it should back it up with prenatal diagnostic services either through referral network or by developing centers within the health system. Screening for trait

13. Cascade screening: Screening of siblings and extended family members of patients and carriers of beta thalassemia. Screening for trait

14. Prevention and control of Hemoglobinopathies in Tamilnadu

15. The morbidity of Hemoglobinopathies is significant among tribals Cost of treatment is very high repeated blood transfusion, iron chelation (Total cost of treating a child in India- 2,10,000INR/child/year ) bone marrow transplant etc Financial and Psychological burden to the family Screening of the carrier status and genetic counseling is important to prevent birth of affected children Rationale

16. School screening program in tribal areas of TamilNadu November 2017 Government Order 337 H & FW (EAP II – 1) dated 22.08.2017

17. Nariyampattu Kalvaran Hills Jolarpet Jamunamathur Alangayam Madhanur Yercaud Harur Pappirettipatti Kolli Hills Uppiliyapuram Thuraiyur Gudalur Udhagamandalam Kothagiri Connoor Anaimalai Karamadai Periyanayakanpalayam Implementation Blocks (Tribal)

18. First Phase - Pilot in 4 Districts – Nov 2017 ( Dharmapuri , Krishnagiri , Namakkal & Salem ) Second Phase –September 2018 – Nilgiris & Coimbatore Third Phase - January 2019 – Vellore , Villupuram & Thiruvanamalai Fourth Phase – Erode , Kannyakumari , Trichy , Dindugal Implementation of the Program ( 30 Blocks in 13 Districts )

19. Training and Modules 4 hands-on workshops conducted. Lab and Doctor’s Module developed

20. Primary Objective To create a community free of Hemoglobinopathies by proactive screening of children by identifying trait & preventing birth of thalassemia and sickle cell anemia children by genetic counseling. Secondary Objective To estimate the prevalence of Hemoglobinopathy carrier ( trait) in the tribal community To provide affordable and adequate therapy to those affected Objective of the Program

21. Implementation Process Description of the Programme

22. Description of the Programme Implementation Process

23. Description of the Programme Implementation Strategy

24. Funding Year Amount (in lakhs) 2016 - 2017 260 2018 - 2019 30 2019 - 2020 60 2020 - 2021 2021 - 2022 60 2022 – 2023 60 TOTAL 500.00 Source :- RoP approval from NHM

25. Once a trait is identified by screening premarital counseling is offered Spouse has to be tested for carrier state either preconception or early ante natal period If the spouse is also a trait , pre natal diagnostic testing like chorionic villus biopsy / amniocenticesis are suggested to find out if the fetus is affected Genetic Counselling

26. Genetic Card

27. Principle : Hb S is insoluble in the reduced state (deoxygenated state) in phosphate buffer solution . It forms tactoids (water crystals) which refract and deflect light rays and produce a turbid solution Solubility test

28. The polymerization of hemoglobin S by reduction or deoxygenation The sickle solubility test reduces hemoglobin S with sodium hydrosulfite . When exposed to sodium hydrosulfite , hemoglobin S from lysed erythrocytes precipitates, causing the solution to become turbid

29. Erythrocytes are lysed by saponin and released haemoglobin is reduced by dithionite in a phosphate buffer. Reduced Hb -S is characterized by its very low solubility and by the formation of nematic liquid crystals ( tactoids ) so that in the presence of Hb -S or non-S sickling haemoglobin , the system becomes turbid

30. Easy to perform V ery useful for mass screening D oes not need a microscope. C ost effective test. The sensitivity is 100% and specificity is about 91%. It has a positive predictive value of 80% and a negative predictive value of 100%. Advantages

31. Take 2 test tubes, fill both with 2ml of working reagent buffer solution Add 2 drops of test sample in one tube Add 2 drops of known negative sample in another tube   Solubility test

32. Hold the tubes against a white paper on which a black line is drawn.   Reading positive negative

33. If it remains clear and dark line can be seen then the test is considered negative If it remains opaque and line cannot be seen then the test is considered positive – i.e Sickle cell trait or sickle cell anemia. Interpretation:

34. No need to make phosphate buffer Ready to use kit. Easy to perform. Eg . Sickle sense Sickleprep . Sickel cell Ready made Reagent sickle solubility test

35. Single tube test Add 1ml of ready made buffer reagent to the test tube provided with the salt Mix well Add 20 microliters of blood. Read line after 5 mins . Sickle solubility test.

36. NESTROFT

37. PRINCIPLE Lowered osmotic fragility is suggestive of Thalassemia trait

38. TEST 2ml of 0.36% saline in one tube 2ml of DW in another tube A drop of well mixed EDTA blood should be added Left undisturbed for half and hour at room temperature. Tubes are held against a white paper on which a black line i s drawn.

39. INTERPRETATION DW tube is clearly visible due to complete lysis Buffered saline : Line visible – test is negative ( hemolysis ) Line not visible- positive (no Hemolysis )

40. Prevalence of Hemoglobinopathies – Trait in Tribal Blocks of Tamil Nadu - India (Nov’17 to Oct’19) Name of District Name of block Proportion of children with hemoglobinopathies among screened Krishnagiri Thally 9.3 Kelamangalam 6.7 Salem Yercaud 10.7 Namakkal Kolli hills 9.0 Dharmapuri Paperettipatty 6.6 Harur 7.4 Coimbatore Karamadai 0.8 Periyanakampalayam,Anaimalai 2.6 The Nilgiris Coonoor 4.3 Gudalur 4.2 Kotagiri 6.6 Udhagamandalam 2.3 Thiruvannamalai Jamnamaruthur 13.3 Vellore Alangayam, Jolarpettai, Anaicut 21.5 Villupuram Kalrayan Hills 9.4 Total 8.7

41. Prevalence of Hemoglobinopathies trait in % Range 0-10 11-20 21-30 Prevalence of Hemoglobinopathies – Trait in Tribal Blocks of Tamil Nadu - India (Nov’17 to Mar’19) Tiruvannamalai

42. IEC at KOLLIHILLS

43. Sampling in the field at Kollihills

44. Sampling in school at Valavanthi , Yercadu

45. Cascade Screening at Denkanikottai , Kelamangalam

46. Results of school screening program

47. Percentage of Carrier positive for Heamoglobinopathy Trait –Cascade screening in Tribal Blocks Outcomes N= 932

48. HPLC machines in 5 medical colleges Increased awareness among tribal population and health care personnel Anemia detection and treatment Establishment of 5 regional day care treatment centres Opportunities

49. Day care centers for treatment of Hemoglobinopathies ICH & HC, Egmore

50. Dharmapuri DAY CARE CENTRE

51. Madurai Day Care Centre

52. Salem Day C are Centre

53. Five more ICHH in 2021 Coimbatore Vellore Vilupuram Trichy Kanniyakumari

54. Antenatal screening

55. Roadmap for AN Screening on Hemoglobinopathies Drawing of Blood from all AN mothers who are attending the AN Clinic during their first visit on Tuesday by the PHC team. Blood samples should be collected in a proper manner 2 samples of 2ml in 2 different EDTA tubes . Written consent should be obtained from all AN Mothers before drawing blood sample. (Target Mothers – 39,000) Using Ice Box and Carrier Boxes samples to be transported under cold chain on the same day to nearby Block PHC where CBC machine is available. Using one of the 2 samples the CBC to be performed by the Block Lab Technician / staff nurse on the same day of testing. CHN to extract the results & values of the CBC in the prescribed format. Another sample should to be transported to the nearest Government Medical College Hospital where HPLC test is done.The samples should reach Medical College by Tuesday/ Wednesday for HPLC testing . Till transport sample should be stored in refrigerator (cold chain). Description of the Program (30 tribal Blocks of13 Districts )

56. Roadmap for AN Screening on Hemoglobinopathies Biochemistry Department of Medical College will test all the samples by HPLC to diagnose positive cases( trait / diseased). HPLC tests will be done on every Wednesday. Details of Positive samples ( of the AN Mother) will be informed to the Block Medical Officer (BMO ), PHC MO, Regular / tribal MMU team , concerned DEIC DDHS , DPH & PM, NHM. The PHC MO should counsel the spouse and arrange to do CBC & HPLC test during the next AN Clinic itself after getting consent. If the spouse is also positive the couple will be counselled by the PHC MO for pre natal diagnosis. He will also ensure that the couple reaches the DEIC where Pre test Counselling will be given for amniocentesis . A separate file should be maintained for each positive couple .The counselling should be video & audio recorded . The couple will be referred to ICH (Genetic Department) for registration and then admitted in IOG for amniocentesis In IOG / BIR where PND is done written consent should be obtained from both the husband & the AN Mothers before doing the amniocentesis. The procedure will be done by the Radiologist / Obstetrician. Genetic Tests for amniocentesis samples is outsourced. The Radiologist / Obstetrician should take all precautions to transport the samples under ideal conditions. Description of the Program (30 tribal Blocks of13 Districts )

57. Roadmap for AN Screening on Hemoglobinopathies If the foetus is affected post test counselling should be given at the DEIC by the DEIC , OG & Paediatric team of the concerned MCH / DHQH genetic team & Haematology team from the state Nodal Center ICH. If the couple wants to terminate pregnancy the MTP will be carried out in the concerned District MCH / DHQ -OG team after getting written consent If the foetus is normal / carrier post test counselling is done in DEIC and pregnancy is continued All babies born to these positive couples should be followed till 6 months of age and HPLC should be done for the baby at the age of 6 th month Note – Amniocentesis is done between 16 – 20 weeks max at 22 weeks . Earlier the better . The Turn around test for genetic testing is 14 working days. Description of the Program (30 tribal Blocks of13 Districts )

58. Instructions for referral to amniocentesis The DEIC MO should give referral slip to ICH Genetic Dept with a copy to IOG Aadhar card should be brought CMCHIS card if available but MTP cannot be refused even if card is not available Should post the details in AN Screening telegram group Attender should accompany the patient preferably a female attender Usually 2 nights stay will be needed Discharge summary should be provided without fail

59. Reporting PHC MO will send a weekly report stating the line list of of AN mothers for whom blood is taken to the concerned Block Medical Officer   Lab technician /DEO in the block will enter the details of the screening tests report and send a copy every week to the concerned PHC MO, BMO , DDHS , Biochemistry Department , DEIC of the concerned district , NHM and DPH (MCH section)

60. Reporting The HOD, Biochemistry should send the HPLC report to the to PHC MO, BMO ,DDHS, DEIC of the concerned district and NHM.  

61. Role of the PHC MO and team IEC of AN mothers and community Collecting blood at PHC after consent and pre-test and post test counselling Ensure blood reaches CHC on the same day . Send a weekly report stating the line list of AN mothers for whom blood is taken to the concerned BMO Follow up the HPLC results regularly. He is responsible for counseling and doing the CBC / HPLC for husband of the carrier

62. Role of the regular MMU team IEC of AN mothers and community Confirms if blood from all antenatal mothers reach the CHC on the same day and CBC is carried out. Ensure blood reaches Medical college on the same day. Regular MMU team will enter the details of the CBC report of all AN mothers in the block and send a copy every week to PHC MO, BMO , DDHS , Biochemistry Department , DEIC of the concerned district and NHM. Follow up the HPLC results of AN mothers. If positive send sample for their spouses(CBC& HPLC) after counselling

63. Role of BMO and team Do CBC for all newly registered antenatal mothers every Tuesday in the block. Make sure CBC machine is functional always and QC is in place. Ensure CBC reports are entered by the CHN and blood reaches Medical college on the same day Follow up of the HPLC reports of all AN mothers in his block BMO along with the PHC MO is responsible for counseling and doing the CBC / HPLC for husband of the carrier and the follow up of husband’s result

64. Role of BMO and team If the spouse also is found to be positive counsel the couple and send them for prenatal diagnosis to the tertiary care centre . Follow up of them till delivery. The Block Medical Officer will maintain a register at the Block on the relevant data for the programme (list of AN mothers who are carriers, list of husband who are positive, list of couples sent for prenatal diagnosis ,final outcome)

65. Role of DEIC DEIC Pediatrician/ Medical Officer will maintain a register on the relevant data for the programme of the whole district ( list of AN mothers who are carriers, list of husband who are positive, list of couples sent for prenatal diagnosis ,final outcome ) Send a monthly report of the above details to NHM in the first week Do both pre test & post test c ounselling for the couples who need prenatal diagnosis and guide them . Audio & Video recording of the counselling should be done. Follow up till delivery . A separate file should be maintained for each positive couple in the DEIC

66. Role of Medical Colleges HPLC testing for all AN mothers, husbands of those who are carriers HOD , biochemistry to send HPLC reports every week to PHC MO, Regular MMU MO, BMO ,DDHS, DEIC of the concerned district DPH and NHM. Prenatal diagnosis- counseling (pre test and post test) and procedure Sending samples for genetic testing appropriately MTP as required Training and supervising the program with the help of DEIC

67. Prenatal diagnosis

68. Prenatal diagnosis

69. Prenatal diagnosis

70. Prenatal diagnosis

71. Amniocentesis procedure in RGGH

72. Funding for AN screening S.NO YEAR OF APPROVAL AMOUNT IN LAKHS 1 2020-2021. 144 2 2021 – 2022 ( 18 Blocks) 215 3 2022 -2023 ( 12 Blocks) 87 446

73. Establishment of Prenatal diagnosis facilities in Govt. Medical colleges Registry for Hemophilia and Hemoglobinopathies Mass screening in Community _National sickle cell mission Future plans

74. Any questions??

75. Thank you

76. Funds Line list of SCA / Thalaseemia – DEIC Portal Sickle Cell Mission