Occurrence of Transfusion Transmitted Infections Among Transfusion Dependent Thalassemia Patients in A Tertiary Care Hospital in India

Background: Blood transfusion is an important treatment modality in the modern health care system; however, transfusion transmitted infections(TTI) could be fatal or life-threatening in some cases. Objective: To determine the occurrence of transfusion transmitted infections among transfusion dependent thalassemia patients and to study the socio-demographic characteristics of the recipients. Methods: This hospital-based descriptive longitudinal studywas conducted between February 2019 and June 2020, on 102 transfusion-dependentthalassaemic patients receiving blood transfusion at Bankura Sammilani Medical College & Hospital, Bankura,West Bengal, India. They were tested for HIV, HBV, HCV, syphilis and malaria by ELISA (Enzyme Linked Immunosorbent Assay) Lisa Scan EM, Merilisa HBsAg, Merilisa HCV, RPR kit and Maleriscan malaria Pf/Pv. Results: Out of 102 patients, 5.90% were positive for TTI. The highest occurrence was found to be of HCV 3.90%. HBV and HIV showed similar occurrence of 0.98% and none came out positive for syphilis or malaria. The highest occurrence of TTI was found among females 66.7%. The average age of the participants was 7.97±3.27years. The average number of blood transfusion received per year was 11.95±2.71units. Majority of the participants belong to low socio-economic group family 62(60.8%). In respect to ethnicity 14.7%were tribal, while 85.3%were non-tribal population. Conclusion : The cause of high prevalence of HCV may be due to donors being asymptomatic in early stages and failure of detection due to window period of infection. More sensitive screening tests should be done for HIV, HBV, and HCV. All donors must be screened by NAT if not possible the patients must be screened for TTI regularly.Thalassemia patients being the most affected, premarital screening for thalassemia should be done.Every patient should be vaccinated with hepatitis B vaccine.


Introduction
FDA defines a TTI as a pathogen that is known to be fatal, to be life-threatening, or to cause severe impairment and that is potentially transmissible through the blood supply. 1 Blood transfusion is an important treatment modality in the modern health care system and though lifesaving but unfortunately it can be one of the sources of infective diseases. 2 A number of blood-borne infectious agents can be transmitted through transfusion of blood and blood products donated by apparently healthy and asymptomatic donors. 3 The diversity of infectious agents includes human immunodeficiency viruses 1 and 2, hepatitis A to E (HAV, HBV, HCV, HDV and HEV), malaria, syphilis, human T-lymphotropic virus types 1 and 2 ( HTLV type 1 and 2) and in certain circumstances cytomegalovirus, parvovirus B19, and many more. [4][5][6] Besides, the established viral, bacterial, and parasitic diseases, novel agents have now appeared and are still emerging as potential threats in transfusion medicine. 7 The most common TTI are due to viral infections. Incidence of bacterial contamination is greatly reduced due to improved collection techniques and use of antibiotics in patients. According to NACO guidelines, all mandatory tests should be carried out on donor's blood samples for HIV, HBV, HCV, syphilis and malaria. 8 In India, it is mandatory to screen donated blood for anti-HIV 1 and 2 (since 1991), anti-HCV (since 2001), HBsAg, syphilis, and malaria.
Blood TTIs mainly occur in patients who are dependent on blood transfusion such as haemoglobinopathies, myelodysplastic syndromes and some haemato-oncology patients, receiving multiple transfusion episodes, either over long periods or over shorter periods. 9 Beta thalassemia major is a hemoglobinopathy also known as Cooley's anemia, is a global health problem characterized by severe hemolysis. 10 Though regular blood transfusion improves the overall survival of patients with β-thalassemia, a definite risk of infection with blood-borne viruses occurs. 11 While in the past it was believed that transfusion transmitted infections were unavoidable, but a low risk of blood supply is expected today. 12 The provision of safe blood for transfusion involves a number of processes, from the selection of blood donors to collection, processing and testing of blood donors by sensitive methods to the testing of patient samples for detection of various infections.

Results
All the 102 participants were tested for HCV antibodies by Merilisa HCV in February 2019 and all were seronegative for HCV. The patients were further tested in August 2019 and showed two HCV positive patients. In February2020, the patients were again tested, and another two new patients were positive as shown in the  Table 3)

Discussion
The probability of acquiring TTIs is related to the probability of being exposed to the infected units of blood. The probability of being exposed to infectious units of blood depends on the number of units transfused and prevalence of carriers among the donor population .Variations in the prevalence of TTIs amongst thalassemics could be related to geographical differences in prevalence of the viral infections among blood donors and the nature of blood donors whether replacement or voluntary. The countries with a higher prevalence of HCV in the general population had a higher prevalence of HCV among thalassemia patients too. 13 There is high prevalence of HCV in thalassemics in all countries because of the unique profile of HCV with very long window period for antibody development.
Our study showed highest occurrence of HCV infection 4/102 (3.90%). The highest prevalence of HCV was also seen in studies like Gugnani et al. 14 of 13.4%, Sidhu et al. 15 of 13.04%, Manisha et al. 16 of 18.2%. Post-transfusion transmission of HCV has still remained a major health concern in multi-transfused patients. Hepatitis B infection was found in one patient out of 102 patients (0.98%). Gugnani et al. 15 found the prevalence of HBV to be 0.79% which was comparable to the present study being 0.98%. Jain et al. 17 showed positivity of 1.04% for HBV.The reduction in the prevalence of HBV may be due to hepatitis B vaccination prior blood transfusion. However, only few studies have been done on transfusion transmitted syphilis and malaria. 15,16 Those two previous studies also found no positive cases for syphilis and malaria, which is similar to our study finding.
The highest incidence of TTI was found among females 66.7% (4/6) in our study, although the male participants were in higher number i.e., 65.7% (67/102). Our finding is notcongruent with the findings ofAhmed Kiani et al. 18 19 Though the cost for NAT testing is considered unaffordable for a medium development country such as India, the burden of TTIs will place an unmanageable cost burden on the society. Now with the introduction of the fourth-generation ELISA test that detects p24 antigen along with antibodies, the window period can be reduced to 2 weeks.

Conclusion
The highest occurrence was found to be HCV which reflects the unsafe practices. The causes of high prevalence of HCV may be due to donors being usually asymptomatic in early stages, despite being screened for HCV possibly due to missing early window period infections. Awareness about screening should be made so that more patients are diagnosed early. Thalassemia patients being the most affected, premarital screening for thalassemia should be done. Screening of all the registered pregnant women for thalassemia status must be done. Parents should be counselled for prenatal testing of thalassemia. Every patient should be vaccinated with hepatitis B vaccine. More sensitive screening tests should be used for HIV, HBV, and HCV. All donors must be screened by NAT if not possible the patients must be screened for TTI regularly. Proper precautions for safe transfusion practices should be adhered to.

Conflict of interest:None declared.
Funding statement: No funding. Authors' contribution:All authors were equally involved in data collection, analysis, manuscript preparation, revision and finalization.