Extended family thalassemia screening as a feasible alternative method to be implemented in identifying carriers in West Java, Indonesia

The thalassemia screening program in Indonesia mostly conducted sporadically. Ideal prospective screening is still limited. This study aimed to compare thalassemia screening methods using the extended family approach with and without a history of severe thalassemia and the feasibility of implementing extended family screening method. A case control study was conducted in Dr. Hasan Sadikin General Hospital Bandung with 3 generations of extended families. Data were collected from 150 subjects of 8 extended families with severe thalassemia as an index case entry and 151 subjects of 12 families with no history of thalassemia. All subjects were examined for Hb, MCV, MCH, and peripheral blood smear (PBS) as initial laboratory examinations. Subjects with MCV < 80 fL, MCH < 27 pg, and suggestive findings on PBS continued hemoglobin analysis. Carrier status was determined by definition. All subjects consented to undergo screening and voluntarily participated. The proportion of thalassemia carriers and the participation rate between the 2 groups were compared. Sixty-four of 150 (42.7%) and 16 of 151 (10.6%) carriers were identified in both the case and control group (p < 0.001). The participation rate was 42–88 vs. 23–100% (p = 0.244). The mean age was 31.9 ± 21.2 vs. 31.1 ± 20.8 years (p = 0.782). The median family size was 28.5 vs. 20 subjects per family (p = 0.245). The types of identified thalassemia carrier in both groups consisted of β-thalassemia, β-thalassemia/HbE, suspected α-thalassemia, and β-thalassemia Hb variant. All carriers continued the counseling process. The extended family method seems feasible to be implemented for thalassemia screening in West Java, Indonesia.

Identification of optimal thalassemia screening strategies for migrant populations in Thailand using a qualitative approach

Background Thalassemia is a common inherited hemoglobin disorder in Southeast Asia. Severe thalassemia can lead to significant morbidity for patients and economic strain for under-resourced health systems. Thailand’s thalassemia prevention and control program has successfully utilized prenatal screening and diagnosis to reduce the incidence of severe thalassemia in Thai populations, but migrant populations are excluded despite having high thalassemia prevalence. We sought to identify key barriers to and facilitators of thalassemia screening and to develop tailored recommendations for providing migrants with access to thalassemia prevention and control. Methods We conducted 28 in-depth interviews and 4 focus group discussions (FGDs) in Chonburi, Thailand with Myanmar and Cambodian migrants, Thai healthcare providers, Thai parents of children affected by thalassemia, and migrant agents. Results Participant narratives revealed that migrants’ lack of knowledge about the prevalence, manifestations, severity, and inherited nature of thalassemia led to misconceptions, fear, or indifference toward thalassemia and screening. Negative perceptions of pregnancy termination were based in religious beliefs but compounded by other sociocultural factors, presenting a key obstacle to migrant uptake of prenatal screening. Additionally, structural barriers included legal status, competing work demands, lack of health insurance, and language barriers. Participants recommended delivering public thalassemia education in migrants’ native languages, implementing carrier screening, and offering thalassemia screening in convenient settings. Conclusions An effective thalassemia prevention and control program should offer migrants targeted thalassemia education and outreach, universal coverage for thalassemia screening and prenatal care, and options for carrier screening, providing a comprehensive strategy for reducing the incidence of severe thalassemia in Thailand and establishing an inclusive model for regional thalassemia prevention and control.

Barriers to Premarital Thalassemia Screening in Asia

Thalassemia is a genetic disorder of hemoglobin synthesis. Every year 70,000 infants are born with beta thalassemia globally. Its incidence can be reduced by premarital thalassemia screening This review aims to focus on barriers to premarital thalassemia screening and to observe the current thalassemia practices in Asian countries. This study was conducted on six countries of Asia based on economic status according to World Bank criteria. High income states included Kingdom of Saudi Arabia, and Oman, Iran constituted an upper middle-income country and in lower middle-income category Sri Lanka, Pakistan and Bangladesh were considered. Search engines like PubMed, Research Gate and Google scholar were used to look for relevant articles from 2005 to 2019. A total of (89) articles were reviewed and (61) articles were finally selected to be included in this review. In Saudi Arabia, major obstacles for premarital thalassemia screening included planned weddings (43%), fear of social disgrace (21%), pressure from family (17%), and religious factors (14%). While in Oman, 4% of the people feared positive results and also considered it as an insult. Amongst the Iranian population, financial burden on couples, disease phobia, fear of positive results, difficulty in accessibility, tribal variances and sociodemographic factors were frequent hindrances to a screening program. Religious factors, financial constraint and lack of awareness cause reluctance in Pakistan and Bangladesh. Moreover, in Sri Lanka, factors like cancellation of marriage and sociocultural norms were identified as negative outcomes of the screening. In conclusion, a negative attitude and reluctant response to premarital thalassemia screening was observed in people belonging to all the countries included. Major contributing factors were religious misconceptions, social stigma, varying ethnicities, low financial status and poor accessibility to screening programs. Key words: Beta thalassemia, thalassemia screening, premarital screening, consanguineous marriage, social impact

Thalassemia and Hemoglobinopathies Screening by Osmotic Fragility (OF) and Dichlorophenol Indophenol Precipitation (DCIP) Tests Among Vocational Students in Ubon Ratchathani Province

Background: Thalassemia and hemoglobinopathies are the most common and clinically serious single gene disorders. Screening by osmotic fragility (OF) test and dichlorophenol indophenols precipitation (DCIP) test have been found to be effective and low-cost approaches to identify those who are carriers especially among young population. Objective: To study the prevalence rates of abnormal of OF test and/or abnormal DCIP test among vocational students in Ubon Ratchathani province. Methods: This cross-sectional research collected data from 311 students aged 15 to 19 years in a vocational school in Ubon Ratchathani, Thailand. OF and DCIP tests were done after participants signed consent to join the study. Knowledge and attitude towards thalassemia and thalassemia screening was obtained from self-administered questionnaires. Chi-square and Fisher exact tests were performed to examine the association between variables. Results: Of 311 students, 124 (39.9%) students had abnormal OF test or DCIP test or both, 72 (23.2%) students had both DCIP and OF tests positive. The final diagnosis was that 75.8% had hemoglobin E, 21.8% and 2.4% were α-thalassemia and β-thalassemia carriers respectively. Approximately, 91.4% of them considered thalassemia screening useful and necessary for premarital screening. Conclusions: High incidence of abnormal OF test and/or DCIP test was found among vocational students in Ubon Ratchathani province, showing a predominance of hemoglobin E. Most of them agreed that thalassemia screening is useful for adolescents to avoid marriage among carriers.

Feasibility of and barriers to thalassemia screening in migrant populations: a cross-sectional study of Myanmar and Cambodian migrants in Thailand

Background Thalassemia, an inherited hemoglobin disorder, has become a global public health problem due to population migration. Evidence-based strategies for thalassemia prevention in migrants are lacking. We characterized barriers to thalassemia screening and the burden of thalassemia in migrant workers in Thailand. Methods Multilingual demographic and KAP surveys were completed by 197 Thai, 119 Myanmar, and 176 Cambodian adults residing in Thailand. Thalassemia awareness, socio-demographic predictors, and knowledge and attitude scores were compared between migrant and Thai subjects. Comprehensive thalassemia testing was performed for migrants. Results Migrants had extremely poor thalassemia awareness (4.1%) compared to Thai subjects (79.6%) and had lower thalassemia knowledge scores but similar attitude scores. Surveys identified differing sociodemographic factors predicting awareness in Thai and migrant subjects, as well as key misconceptions likely to hinder thalassemia screening uptake. Nearly all migrants consented to thalassemia testing. We identified abnormal hemoglobin profiles in 52.7% of migrants and a higher projected rate of severe thalassemia births in migrants. Conclusions The high burden of thalassemia and tremendous knowledge gap in migrants needs urgent attention. Thalassemia screening was feasible and acceptable in our migrant population. Sociocultural and structural barriers merit further attention when designing thalassemia screening and prevention policies for migrants in Thailand and globally.

In silico prediction of HBD gene variants in the Iranian population

Background The quantification of hemoglobin A2 (Hb A2; α2δ2) is used as a valuable test to differentiate α- and ß-thal carriers in clinical laboratories. Therefore, the HBD (δ-globin) gene variants could result in reduced levels of Hb A2 and have implications for thalassemia screening programs. The aim of the present study was to predict the consequences of HBD gene variants identified in the Iranome project. Results The highest number of variants was in the Persian Gulf Islanders. The variants of p.Gln132Glu (HBD: c.394C>G), p.Gly17Arg (HBD: c.49G>C), p.Thr5Ile (HBD: c.14C>T), and p.Ala28Ser (HBD: c.82G>T) presented damage results in three or more prediction tools. In addition, it seems that the p.Gly30= (HBD: c.90C>T) decreases the use of authentic splice and, instead, creates a new donor splice site (DSS) or leads to the use of a cryptic DSS. Conclusions Most of these variants have been associated with a decrease in Hb A2 levels. Due to the high mutational diversity in the HBB gene in the Iranian population and the use of Hb A2 quantification to differentiate α- and ß-thal carriers among Iranian clinical laboratories, some attention should be taken to a possible co-inheritance of HBD gene variants to avoid the misdiagnosis of ß-thal carriers.

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

BACKGROUND: β-thalassemia is an inherited blood disorder that relatively common in Southeast Asian countries. In Indonesia, it is estimated that 200,000 infants with thalassemia carrier born each year. Mutation causing β-thalassemia is highly varied and relatively specific in a population. This study aimed to identify the mutations responsible for β-thalassemia from Thalassemia Carrier Screening conducted in Yogyakarta Special Region. This information is beneficial for developing a strategic prevention program to control thalassemia in the region.METHODS: Twenty-eight blood samples of haematologically suspected β-thalassemia from participant of thalassemia screening program in Yogyakarta Special Region were investigated for β-globin gene mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS) and DNA sequencing.RESULTS: Our samples showed average HbA2 value of 5±0.81% and HbF value of 2±2.29%. It showed eight abnormal erythrocyte morphologies dominated by hypochromia (96.4%), cigar cell (85.7%), and microcytosis (78.6%). Our molecular investigation identified three splice-site mutations namely InterVening Sequence (IVS)-1-5 (G>C) (71.4%), IVS-1-2 (T>C) (7.1%), and IVS-1-1 (G>T) (3.6%), two frameshift mutations that are CD35 (-C) (10.7%) and CD8/9 (+G) (3.6%), and a missense mutation of CD6 (GAG>GTG) (3.6%).CONCLUSION: Our study concluded on a high prevalence of IVS-1-5 (G>C) mutation in Yogyakarta Special Region. This mutation information is significant for developing a strategic prevention program to control thalassemia in the region, for example for developing a rapid molecular test for future screening program.KEYWORDS: β-Globin gene, thalassemia, screening, carrier, mutation, Yogyakarta

Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran

Background: Beta-thalassemia minor and thalassemia major are an autosomal recessive disease with hypochromic, microcytic anemia, and morbidities, Today, therapeutic advances have significantly improved the life expectancy of thalassemia major patients, but at the cost of financial toxicity. The present study aimed to investigate the possibility of increasing the funding for thalassemia screening programs and comparing the cost-effectiveness of screening for thalassemia in the treatment of the patients. Methods: In this study, screening for thalassemia minor was compared with the treatment of thalassemia major patients. A decision tree model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. The approach of purchases of services was used to evaluate the screening test costs for patients with thalassemia major. Also, a bottom-up method was applied to estimate other screening and treatment costs. All the costs were calculated over one year. The number of gained quality-adjusted life years (QALYs) was calculated using the EQ-5D questionnaire in the evaluated patients. Results: In this study, 26.97 births of patients with thalassemia major were prevented by screening techniques. On the other hand, total screening costs for patients with thalassemia major were estimated equal to US$ 879879, while the costs of preventing the birth of each thalassaemia major patient was US$ 32 624 by screening techniques. In comparison, the cost of managing a patient with thalassemia major is about US$ 136 532 per year. The life time QALYs for this is 11.8 QALYs. Results are presented using a societal perspective. Incremental cost per QALY gained with screening as compared with managing thalassaemia major was US$ 11 571. Conclusion: Screening is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of managing thalassaemia major patients.