An estimated 1.5% of the global population are thalassemia carriers, with varying clinical heterogeneity.1 Thalassemia is considered a major public health problem in Pakistan, with a carrier rate of approximately 5%. Over 5000 new cases of beta-thalassemia major (TM) are diagnosed annually.2 In an approximate population of 182 million people in Pakistan, there are six major ethnic groups: Punjabi (53.5%), Pashtun (Pathan) (15%), Sindhi (14%), Muhajirs (7.5%), Balochi (3.5%) and others (6.5%).3

The hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common transfusion-transmitted infectious agents which became known in 1963 and 1975, respectively.4 Globally,2 billion people are positive for HBV. The World Health Organization (WHO) has declared South Asia as a high-risk area for HCV, with a prevalence rate of 2.1%.5 In Pakistan, the prevalence rate of HBV is 3–5% and of HCV, 4–5%.6 The asymptomatic spread via parental transmission is the root cause of its transmission in early childhood. There is a strong belief that lack of implementation of international standards for blood transfusion and its practices, including syringes and shared equipment, such as shaving kits, and percutaneous injuries are the main contributors toward their widespread infection.7

Failure in the prevention of thalassemia has resulted in an ever-growing demand for blood transfusions. High transfusions rates increase TTI risks, thereby limiting the life expectancy.8,9 Limited resources and lack of awareness are constantly hindering the improvement in the current alarming situation. Therefore, better practices in both governmental and private sectors are required. A national vaccination campaign against HBV has been initiated, principally at the neonatal level, with approximately 73% of the neonates having been vaccinated.10 Frequent vaccination is an utmost necessity for its prevention, but unfortunately, scarce studies have been reported to date from rural areas of Pakistan.8,9,11 In thalassemia major, regular blood transfusion is required to keep a pre-transfusion hemoglobin (Hb) level at 9–10.5g/dL.12 Therefore, iron chelation therapy is obligatory to avoid fatal organ damage.

The WHO has reported an approximate 1.5 million annual blood transfusions in Pakistan.13 It is our social dilemma that most of the donors hide their health status from relatives and willingly contribute to blood donation. However, donors must be repeatedly checked for negative results for bloodborne pathogens.8 Careful selection criteria for donors, proper blood screening and standardized safe procedures for blood storage and maintenance are some of the measures that can be adopted to minimize viral transmissions. Although public health authorities are raising awareness among the general and high-risk populations, with the assistance of electronic and print media, yet these efforts are not practiced in most Pakistani rural areas.9,11,14 Therefore, this study, in addition to determining the seroprevalence, also aims to identify those sociodemographic and clinical pitfalls that have contributed to the persistent prevalence of TTIs, regardless of the presence of safe transfusion guidelines.

Thalassemia is the prevailing single-gene disorder in more than 60 countries in the world. Regular transfusion is the only available approach, in addition to bone marrow transplantation (BMT). Inefficacy in preventing thalassemia has been constantly increasing the demand for blood transfusions and therefore, the chances of developing TTIs, as well.8,9 The risk of TTIs is the main concern for both practitioners and subjects. As recommended by the World Health Organization (WHO), the screening of blood or blood products should be performed at least for HCV, HIV, HBV, malarial parasites and syphilis.13,16 There are not many studies from Pakistan that determine the TTI seroprevalence rates and their contributing factors. Therefore, a multicenter study representing different localities and analyzing them for various aspects would be of interest in awareness regarding the functionality of blood safety measures. Seroprevalence rates of 10% for HBV and 32.9% for HCV were comparable to those of previous studies.8,9,14,17 The incidence rates can be correlated with the fact that, due to transfusion, TDT subjects are usually more prone to HBV infections. However, with the advances in HBV vaccination, a dramatic decrease in the global incidence rate has occurred.9,14,18

Statistically significant (p=0.001) differences among seroprevalence rates in different provinces support the earlier findings that different ethnicities and cultures and their underlying differences are also considered as risk factors.19,20 In the present study, the prevalence of TTIs in all three provinces might be due to poor hygienic and health conditions at home.21 A high consanguinity rate is one of the substantial factors in the spread of thalassemia. Resembling the previous reports, this study also observed that males (51.4%) were significantly (p-value=0.003) more affected than females (20.4%). A high prevalence of viral infections is due to the poor provision of basic necessities, particularly access to clean water and proper sanitary setups for common people.18,22

The presence of hepatitis infection puts obvious financial strain on the families. The elevated risk of trans-transmission among family members was similar to that previously reported by Din et al.,9 and Qurat-ul-Ain et al.,23. Likewise, Saeed et al.,17 found that the first child in a family suffering from thalassemia was seropositive in a higher number of instances. Thalassemia subjects coming for transfusion at the different transfusion centers in Pakistan were initially screened for seroprevalence.

The TTI seroprevalence was higher in individuals at a transfusion center that was not self-sufficient in its blood supply. This is due to the fact that blood is supplied by volunteer donors (replacement donors), in most cases close relatives. This frequent practice may have played a vital role in TTIs. Behavior-based donor selection will be helpful in sensibly minimizing this risk. Therefore, repetitive negative screening for TTIs in blood donors should be included. Unfortunately, all of these practices rely on the honest disclosure of risk behavior, putting aside all fear of stigmatization. Therefore, in addition to assessing TTIs, measures should also target the awareness, attitude and behavior of blood donors and recipients. This will be helpful in setting special measurements and priorities, according to region studied, for the implementation of preventive strategies. This would ultimately improve the public health and, hence, would lead to a rise in blood safety and quality for donors, recipients and transfusion centers.20,21 The low rate (78, 22.3%) of thalassemia-related deaths in family histories reflects the insufficient public awareness of the clinical picture of thalassemia in past.

A comparatively high demand for transfusion is due to poor clinical management, increased iron overload, splenomegaly, very distant transfusion centers and/or an inadequate blood supply. As reported in previous studies, seroprevalence in our study was high in subjects ≥10 years of age due to an increased transfusion frequency leading to iron-related complications.9,17 High transfusion frequency (p=0.043) and increased ferritin levels (p=0.003) are significantly associated with TTI seropositivity, as also observed in earlier studies.8 A major improvement in the public sector is thus required. Implementation of good practices along with increased public awareness will subsequently lessen the TTI burden, as it was observed that the number of seropositive subjects was lower in the ≤10 years of age group compared to the ≥10 years age group. However, it is also a fact that the low number of transfusions in the ≤10 years old of age group compared to the ≥10 years old contributed to the low frequency of TTIs. Meanwhile, productive outcomes are turning up, such as the adoption of the HBV screening program initiative in 1994, which was evidenced by the decreased number of cases reported in a group of subjects with FBT at age ≤10 years.9,14 Similarly, with frequent transfusions (4/8 weeks), the number of thalassemia subjects with HCV and/or HBV infections has increased twofold, but this association was non-significant.17

The results in the present study were in accordance with previous reports, however minor differences could be due to the sample size, region studied and blood source availability and systems implemented for its screening and transfer to the subjects. The differences can be attributed to the confidence interval (CI) that is not narrow. Asymptomatic spread via parental transmission is the main transmission route in early childhood. In addition, lack of implementation of international standards in blood transfusion and its practices, unsterilized syringes, shared equipment, such as shaving kits, and percutaneous injuries have also contributed to its widespread occurrence.8,11 In the absence of any available treatment for thalassemia, standardized health codes assure better health settings. TTI-infected subjects must be periodically monitored and awareness campaigns must be conducted to increase understanding of the epidemiological pattern and risk associated with its spread.8

The HCV is the most prevalent TTI in thalassemia major in our study. Therefore, a self-sufficient and safe blood supply with improved blood screening and donor selection is required to minimize TTIs.Furthermore, raising awareness with the assistance of electronic and printed media will also be beneficial.

The authors declare no conflicts of interest.