The epidemiology of thalassaemia syndromes in Southeast Asia

Summary

Thalassaemia syndromes are inherited haemoglobin disorders caused by mutations affecting α- and β-globin chains, ranging in severity from asymptomatic to transfusion-dependent. This Series paper synthesises epidemiological data across ten WHO Southeast Asia Region (SEAR) countries, combining local expertise with a rapid literature review. Due to the high prevalence of α- and β-thalassaemia variants, as well as haemoglobin E, the SEAR carries a disproportionately high burden and faces specific challenges. Although a small number of mutations tends to dominate in each country, the range of underlying mutations and deletions is complex. Beyond molecular studies, epidemiological data remain limited in most SEAR countries. Key challenges include blood supply shortages, consanguinity, gender-based disparities in healthcare access, population migration redistributing mutation profiles, and poor awareness. Recommendations to reduce the health burden of thalassaemia syndromes in the SEAR include setting up national registries, expanding premarital and prenatal screening, improving blood supply coordination, and promoting culturally sensitive education. Without targeted investments and policy commitment, most SEAR populations will remain unable to benefit from recent therapeutic advances, including emerging gene therapies.

Introduction

The thalassaemia syndromes represent a complex group of inherited haemoglobin disorders.¹ Hundreds of genetic mutations and deletions–on chromosome 16 for α-thalassaemia and on chromosome 11 for β-thalassaemia–lead to syndromes ranging from asymptomatic to extremely severe. The severity of the thalassaemia syndromes is usually driven by the imbalance between the production of α-globin and β-globin which are required to produce normal haemoglobin (Hb).² Clinically significant forms of α-thalassaemia include haemoglobin H (HbH) disease–non-deletional variants being more severe than deletional ones–and haemoglobin Bart's hydrops fetalis.³ The most clinically significant forms of β-thalassaemia (or thalassaemia major) involve the total absence of β-globin (β⁰β⁰). Individuals inheriting a β⁰ variant, alongside a β+ polymorphism (β⁰β⁺) or HbE (β⁰β^E), present a range of clinical severity from thalassaemia intermedia to thalassaemia major.⁴ HbE is one of the most common structural haemoglobin variants globally, alongside HbS and HbC. Severe thalassaemia syndromes require lifelong regular blood transfusions for survival and, as such, they are often referred to as transfusion-dependent thalassaemia (TDT).⁵ Syndromes requiring only occasional transfusions or regular transfusions for a limited period are termed non-transfusion dependent thalassaemia (NTDT).⁶

The global health relevance of the thalassaemia syndromes is increasing for several reasons.⁷ The number of people affected by thalassaemia syndromes globally is increasing, as areas of high prevalence, such as Southeast Asia, are largely populated and life expectancy tends to improve. Many of the affected individuals remain undiagnosed, since newborn or premarital screening is still limited in many high burden countries.^8,9 As a result, care for patients with thalassaemia is often weighted more towards managing chronic complications rather than on preventive interventions, and curative options are still not available to the majority of patients with a thalassaemia syndrome.^10,11 In addition, management of severe thalassaemia syndromes relies largely on blood transfusions, which are particularly affected by shortages and safety issues across most low- and middle-income countries (LMICs).¹² Finally, global population movements mean that cases of severe thalassaemia can now be identified in many non-endemic regions, such as the United States or Northern Europe.¹³

Although α-thalassaemia and β-thalassaemia occur worldwide, severe syndromes are particularly prevalent in Southeast of Asia,⁹ where HbE β-thalassaemia is also common.¹⁴ The main hypothesis for this high prevalence of thalassaemia variants is positive selection due to protection against severe malaria.^15,16 A quarter of the world's human population lives in the World Health Organisation (WHO) Southeast Asia Region (SEAR), which faces significant health challenges alongside growing socio-economic disparities.

Despite substantial advances in the management of thalassaemia syndromes, including substantial reductions in disease burden in some parts of the world and the rapid development of gene therapies offering promising curative opportunities, the thalassaemia syndromes remain largely neglected and underfunded.^11,17 As a result, populations living with these disorders across SEAR have seen little benefit from these improvements. Considering the high individual and societal cost and their impact on quality of life,¹⁸ greater awareness, routine testing, and better access to safe blood for transfusion, iron chelators and standardised high-quality clinical management would likely offer great benefits both to affected populations and to local economies across the region.²

The aim of this Series paper is to provide an overview of the epidemiology of the thalassaemia syndromes across the SEAR, highlighting some of the specific challenges faced by countries considered, and providing recommendations to address the key knowledge gaps identified.

Search strategy

This Series paper focuses on the ten SEAR countries: Bangladesh, Bhutan, the Democratic People's Republic of Korea, India, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste. Indonesia moved from the SEAR to the Western Pacific Region (WPR) at the end of 2025.¹⁹

To compile this paper, we contacted national experts in each of these countries and requested each to write a section compiling the data available on the epidemiology of thalassaemia syndromes in their country. No experts could be identified in the Democratic People's Republic of Korea and in Bhutan. This expert synthesis was complemented by a rapid review of the literature on the epidemiology of thalassaemia syndromes in SEAR. We opted for a rapid rather than a full systematic review because a substantial proportion of relevant epidemiological data is published in local languages and they do not tend to be indexed in international databases. Identifying and retrieving this literature would have required in-country staff in each country covered by this review, which was beyond the scope of this work. Our approach followed the interim guidance for the reporting of rapid reviews published by the Cochrane Rapid Reviews Methods Group.²⁰

A search was conducted in PubMed, using the following MeSh terms: “thalassemia” AND (“prevalence” OR “incidence” OR “mortality”) AND (“Bangladesh” OR “Bhutan” OR “Democratic People Republic of Korea” OR “India” OR “Maldives” OR “Myanmar” OR “Nepal” OR “Sri Lanka” OR “Thailand” OR “Timor-Leste”) on 1st June 2026. Only studies of humans were considered. Searches covered all years (1969–2026), with no restrictions on country or language of publication. References identified were exported into Covidence for review and analysis. Restricting the search to PubMed is a limitation of this review, as relevant studies indexed only in regional or non-English-language databases may have been missed; we sought to mitigate this by complementing the search with expert-contributed country sections. Although we have previously shown that substantial additional data are available through local sources (e.g. national journals or unpublished reports), often not in English,²¹ it was beyond the scope of this review to collect such data across the ten countries considered.

Our search identified a total of 769 references (Figure S1). Almost half of these (49%) were published after 2015. Based on a quick review of the title and abstract (conducted by a single assessor), we excluded 256 references which i) were not related to the thalassaemia or a SEAR country; or ii) did report on individual cases; or iii) covered purely laboratory techniques. Out of the remaining 513 references, we further excluded 259 references which were not relevant to the epidemiology of the thalassaemia in our SEAR countries, including descriptions of specific complications in thalassaemia patients, specific treatment or therapies, or methodological studies. Full texts of references included were only collected and used to expand on evidence available in the abstracts. The vast majority of the 254 references included related to India (n = 124) and Thailand (n = 91). The number of references included for Bangladesh (n = 9), Maldives (n = 2), Myanmar (n = 4), Nepal (n = 6) and Sri Lanka (n = 14) was limited. No references were identified for Bhutan, the Democratic People Republic of Korea or Timor Leste, reflecting the particular lack of internationally accessible data on the epidemiology of thalassaemia in these three countries. The remaining four references included were relevant to several SEAR countries.

Genetics and severity

Amongst the multitude of thalassaemia variants identified worldwide, a few largely dominate across the SEAR, which is consistent with population genetics concepts of founder effects and historical population isolation. In most of the countries considered, molecular studies to quantify the frequency of the underlying genetic variants for α- and β-thalassaemia have been conducted, but they vary in size (Table 1).

Table 1.

Overview of the frequency of the main genetic variants of α- and β-thalassaemia identified in studies conducted in countries of the Southeast Asia Region (SEAR).

		Bangladesh	Bhutan	D.P.R. Korea	India	Maldives	Myanmar	Nepal	Sri Lanka	Thailand	Timor Leste
α-thalassaemia
α+	−α3.7	4.9	/	/	12.8	/	43.7	53.1	6.5	20.4	/
α+	−α4.2	1.7	/	/	0.1	/	1.5	3.7	1.1	1.7	/
α0	--SEA	4.4	/	/	/	/	2.3	/	/	48.4	/
α0	--THAI	0.7	/	/	/	/	/	/	/	0.6	/
α0	--MED	1.0	/	/	/	/	/	/	/	/	/
	αCS	/	/	/	/	/	2.3	/	/	24.7	/
	αPS	/	/	/	/	/	/	/	/	2.4	/
/	Others	/	/	/	/	/	/	/	/	2.0	/
Source & sample size		n = 4089	/	/	N = 79813	/	n = 34122	n = 8123	n = 45420	n = 80324	/
β-thalassaemia
β0	IVS-I-1 (G > A)	/	/	/	/	12.0	/	/	15.2	/	/
β0	IVS-I-1 (G > T)	/	/	/	6.2	0.2	1.8	3.5	0.4	4.7	/
β+	IVS-I-5 (G > C)	39.1	/	/	54.7	77.6	0.6	31.6	56.2	9.2	/
β0	IVS-I-130 (G > C)	1.6	/	/	/	/	/	/	0.7	/	/
β+	IVS-II-654 (C > T)	/	/	/	/	/	/	/	/	2.6	/
β0	619del	0.8	/	/	10.0	/	/	29.8	0.1	/	/
β0	Cd 5 (-CT)	/	/	/	0.9	/	/	/	0.1	/	/
β0	Cd 8/9 (+G) / FS8.9	2.7	/	/	5.5	0.1	/	21.1	1.3	/	/
β0	Cd 15 (G > A)	1.9	/	/	5.5	0.2	/	/	0.6	/	/
β0	Cd 15 (-T)	1.6	/	/		/	/	/	2.2	/	/
β0	Cd 16 (-C)	0.8	/	/	0.8	/	/	10.5	1.6	/	/
β0	Cd 17 (A > T)	/	/	/	/	/	0.6	3.5	/	13.4	/
β+	Cd 19 (A > G)/Hb Malay	/	/	/	/	/	/	3.5	/	5.3	/
β+	Cd 26 (G > A)	40.2	/	/	/	/	/	29.8	13.1	22.1	/
β0	Cd 30 (G > C)	3.5	/	/	2.6	15.6	/	/	0.9	/	/
β0	Cd 30 (G > A)	1.6	/	/		/	/	/	/	/	/
β0	Cd 35	/	/	/	/	/	/	/	/	0.5	/
β0	Cd 41/42 (-TTCT)/FS 41/42	4.3	/	/	6.1	0.9	/	4.9	3.1	25.1	/
β0	Cd 71/72 (+A)	/	/	/	/	/	/	/	/	2.7	/
β+	-90 (C > T)	1.9	/	/		/	/	/	/	/	/
/	Others	/	/	/	6.5	/	/	/	2.8	10.6	/
/	Unknown	/	/	/		/	0.3	/	1.7	3.5	/
Source & sample size		n = 25610	/	/	n = 425012	n = 110,50414	n = 34122	n = 6118	n = 62020	n = 113824	/

Data based on patient cohorts for which the total of proportions of all variants adds up to ∼100%, are italicised.

In a study of 413 newborns in Bangladesh, the –α^3.7 and --^SEA deletions were found to be the most prevalent heterozygous deletions, representing 4.9% and 4.7%, respectively, of all subjects.²⁵ The frequency of the – α^4.2, --^MED and --^THAI mutations was 1.25%, 0.98% and 0.74%, respectively. No case of HbH disease or Hb Bart's hydrops fetalis was identified. In another study of 256 Bangladeshis, the most common β-thalassaemia mutations were Cd26 (G > A) (40.2%) and IVS-I-5 (G > C) (39.1%). The β⁰ variants Cd41/42 and Cd30 had frequencies of 4.3% and 3.5%, respectively.²⁶ Amongst 1063 patients studied with a complete medical record, 91.3% required blood transfusions, with 67.0% of them being TDT, and 24.4% being NTDT.²⁷

In India, a meta-analysis of 17 studies including 8505 alleles with near national coverage revealed that 52 mutations accounted for 97.5% of all β-thalassaemia alleles. The prevalence of the commonest mutation IVS-I-5 (G > C) varied from 44.8% in the North to 71.4% in the East.²⁸ Over 80 β-thalassaemia mutations have been identified in large studies from different regions which included many rare and some novel mutations while many have been individual case reports. The most common α-thalassaemia variants are the 3.7 kb (−α^3.7) and 4.2 kb (−α^4.2) deletions. HbH disease is much less frequently seen among Indians and Hb Bart's hydrops fetalis is rarely ever reported.²⁹ Triplicated α genes are seen in 1–2% of individuals.

Maldives is the only country in the region with a national thalassaemia screening programme, established in the early 1990s. Between 1992 and 2015, more than 110,000 individuals were screened, and molecular genetic testing was subsequently conducted on 874 identified β-thalassaemia carriers. The most common mutations were IVS-I-5 (G > C) (77.6%), Cd30 (15.4%) and IVS-I-1 (G > A) (9.0%).³⁰ At the end of 2025, there were 459 patients with TDT β-thalassaemia, 88 with NTDT, and 82 with HbE/β-thalassaemia known patients across Maldives.

In Myanmar, it is estimated that 1.0–4.9 per 1000 live births is affected by a major haemoglobinopathy. In a 2002 study, 19 β-thalassemia mutations (14 β⁰; 5 β⁺) were characterised.³¹ The most common mutations identified were: IVS-I-1 (G > T) (28.2%), Cd41/42 (23%), IVS-I-5 (G > C) (15.3%) and Cd17 (A > T) (9.1%).³² Amongst 170 TDT patients, three α-thalassaemia deletions were found to be common: −α^3.7, −α^4.2 and --^SEA. Hb Constant Spring (CS) is the only reported mutational α+ variant in Myanmar. Based on hospital data, β-thalassaemia major, HbE/β-thalassaemia and HbH disease represent 5–22%, 46–58%, and 6–37% of cases, respectively.³³ No cases of Hb Bart's hydrops fetalis have been reported.

A study of 61 thalassaemia patients from 17 ethnic groups across Nepal identified nine different β-thalassaemia mutations, with the most prevalent being Cd26 (G > A) (18%), IVS-I-5 (G > C) (14.8%), 619del (11.8%), and Cd16 (-C) (9.8%).³⁴ An early study in lowland areas of Nepal found that the main α-thalassaemia variant was −α^3.7, with the −α^4.2 being only found in one of the ethnic groups studied (Newar).³⁵

In a study of 620 patients from Sri Lanka, three mutations accounted for 84.5% of β-thalassaemia alleles: IVS-I-5 (G > C) (56.2%), IVS-I-1 (G > A) (15.2%), and HbE (13.1%), while the frequency of α⁺ deletions was ∼6.5% for −α^3.7 and ∼1.1% for −α^4.2.³⁶ Non-deletional variants of α-thalassaemia are rare. Homozygosity or compound heterozygosity for the β⁰ mutations IVS-I-5 and IVS-I-1 is typically associated with TDT.¹⁴ In contrast, HbE/β-thalassaemia accounts for approximately 30–40% of cases and demonstrates marked phenotypic variability.

Finally, in Thailand, the most prevalent β-thalassaemia mutation is CD41/42, which accounts for approximately 30% of β-thalassaemia alleles nationwide. Regional variations have been observed with the IVS-I-5 (G > C) mutation and Cd19 (A > G) mutation being particularly common in southern Thailand, whereas the Cd17 (A > T) mutation is more frequently observed in northern parts of the country. Deletional mutations account for the vast majority (∼75%) of α-thalassaemia cases in the Thai population. The most prevalent α⁰-thalassaemia mutation is the Southeast Asian deletion (--^SEA), whereas the Thai deletion (--^THAI) is encountered much less frequently, accounting for less than 0.5% of cases. Two major forms of α⁺-thalassaemia have been identified in Thailand: −α^3.7 (∼95%) and −α^4.2 (<5%). HbE is particularly common in the region bordering Laos, and Cambodia.

Sickle cell anaemia (HbSS) and sickle β-thalassaemia (HbS/β-thalassaemia) are also present in sub-populations across India³⁷ and the western part of Nepal,³⁸ but sickle cell disease is rare in the other SEAR countries.

Prevalence and incidence

Detailed epidemiological estimates of the burden of the thalassaemia syndromes are lacking in most countries worldwide. Despite new studies conducted over the last two decades providing additional data,¹³ and substantial developments in geospatial and statistical methods to assess disease burden and reflect uncertainties,³⁹ estimates produced by Modell and Darlison⁴⁰ remain the only ones providing a comprehensive assessment of the burden of α-thalassaemia and β-thalassaemia in all countries worldwide. More recent estimates, such as those produced by the Global Burden of Disease (GBD),^9,41 do not differentiate between these two main categories of thalassaemia syndromes and often rely on generic methods, rather than approaches tailored to their specificities. Producing reliable estimates of the burden of these syndromes is challenging because of their complexity and of the substantial variability in their distribution over relatively short distances.⁴² This has been illustrated in several micromapping studies conducted across the SEAR.43, 44, 45 As shown in Fig. 1, the burden of the thalassaemia syndromes does not depend only on population size, but also on the prevalence and severity of the genetic variants present in each country. For example, Maldives has the smallest population in SEAR, but it has one of the highest estimated prevalence and mortality rates.

Fig. 1.

Population estimates for 2026 from the UN World Population Prospects 2024, alongside the age-standardised prevalence, incidence and mortality rates (ASPR, ASIR and ASMR, respectively) from Tuo and colleagues⁴¹ for the SEAR countries in order of decreasing population. Rates are shown on the left-axis. Population (in thousands) is shown on the right-axis. ASMR have been multiplied be 10 to help with their visualisation alongside the other rates. Uncertainty estimates are shown in Table S1. D.P.R.: Democratic People's Republic.

Modell and Darlison estimated that, across the SEAR, 43.7% of pregnant women carried an α-thalassaemia variant and 4.2% were carriers of a β-thalassaemia variant or HbE.⁴⁰ These estimates are not up-to-date and do not include any measure of uncertainty. In the GBD study, Tuo and colleagues estimated the age-standardised prevalence rate of thalassaemia in SEAR to range from 4.5 (95% Uncertainty Interval (UI): 3.6–5.8) in India to 157.1 (95% UI: 126.8–195.6) in Thailand (Table 2). Although such estimates aim to facilitate comparisons and include measures of uncertainty, they are difficult to put in perspective with data from local studies.

Table 2.

Overview of the population size and prevalence of thalassaemia syndromes in countries of the Southeast Asia Region (SEAR).

Country	Population (M)a	Carriers	Thal major annual births (Modell & Darlison, 2006)b		Clinically relevant syndromes		Source(s)
			α-thal	β-thal	TDT	NTDT
Bangladesh	176,757 [175,957–177,556]	17–22 M	0	2125	a: 2000	a: 8000	36
Bhutan	799 [796–803]	na	0	0	na	na	/
D.P.R. Korea	26,605 [26,511–26,699]	na	na	na	na	na	/
India	1,470,296 [1,464,501–1,476,091]	35–45 M (β) na (α)	0	5307	na	na	46
Maldives	531 [529–532]	∼66,000	0	52	1000		14
Myanmar	29,608 [29,468–29,748]	∼1.3 M	74	2410	a: 52–155 (β) a: 1030–1670 (α)	a: 18,700–135,000 (β) a: 21,000–28,000 (α)	Win (pers.com.)
Nepal	23,290 [23,209–23,372]	∼1 M	0	116	>54	na	18
Sri Lanka	55,022 [54,814–55,229]	∼500 k	0	179	2500		47
Thailand	71,593 [71,354–71,832]	18–34 M	2291	3070	a: 4250 (α/β)	336,000	24
Timor Leste	1427 [1422–1433]	na	na	na	na	na	/
SEAR (%)	702,434 [699,839–705,030]	73–104 M	2365 (24.9%)c	13,259 (31.6%)c
WORLD	8,266,245 [8,237,154–8,295,335]	/	9483	41,930

a: annual; α: α-thalassaemia; β: β-thalassaemia; D.P.R.: Democratic People's Republic; M: million; na: not available; SEAR: Southeast Asia Region.

^aEstimates (mean [low-high]) from the United Nations World Population Prospects 2024 for 2023.

^bRecalculated for 2023 based on demographic data from the United Nations World Population Prospects 2024.

^cProportion of the world estimate or count.

The carrier frequency of thalassaemia syndromes in Bangladesh varies between 10.9% and 13.3%. Studies estimated the prevalence of α-thalassaemia syndromes to be around 16%,²⁵ while the carrier prevalence of β-thalassaemia and HbE is thought to be 2–3% and 8–10%, respectively.⁴⁸ HbE β-thalassaemia are thought to represent around 70% of β-thalassaemia patients in Bangladesh. According to the National Thalassaemia Survey 2024 report (based on a nationally representative survey of individuals aged 14–35 years from 8680 households), the highest prevalence of thalassaemia carriers in Bangladesh is found in the Northwest (Rangpur Division: 27.7%, Rajshahi Division: 11.3%) and in the Southeast (Chattogram Division: 11.2%). The lowest prevalence is in the Northeast (Sylhet Division: 4.8%).⁴⁸ Researchers estimated that nearly 17–22 million people are thalassaemia carriers and that 70,000 patients are suffering from thalassaemia syndromes. Around 10,000 new births are estimated to be affected each year, including over 2000 TDT cases.⁴⁸

The average prevalence of α-thalassaemia carriers in India is around 13% among the non-tribal populations and ranges from 17% to 97% in tribal populations. Many studies across India, including large ones (e.g. n = 287,258 in Maji et al.),⁴⁹ have revealed an average prevalence of β-thalassaemia carriers of 3.7% (95% CI: 2.5%–5.0%) in the general population, and 4.6% (95% CI: 3.2%–6.2%) in tribal groups.^46,50 Based on this, it is estimated that there would be between 35 million and 45 million carriers of β-thalassaemia in India alone. A prevalence of HbE carriers of 20–64% has been reported in the North-Eastern region of India (Assam, Meghalaya and Tripura), compared to 3–10% in the eastern state of West Bengal. As of July 2025, 4361 thalassaemia patients, including 2579 children under the age of 12 years, have been registered through the National Sickle Cell Elimination Mission in India.⁵¹ Although this only represents a small proportion of the thalassaemia population across the subcontinent, it provides a first national database with consistent information across states. The March of Dimes Global Report on Birth Defects suggested that 1.2 per 1000 live births in India were affected by pathological haemoglobinopathies, corresponding to 32,400 babies with a severe haemoglobin disorder born each year (based on 27 million annual births at that time).⁵² In 2026 (23 million annual births), this would still represent 27,600 babies being severely affected.

A large study of 110,504 individuals (∼30% of the entire population) was conducted as part of the National Thalassaemia Screening Programme between 1992 and 2015 across the 20 atolls of Maldives. The study reported one of the highest carrier rates of β-thalassaemia (16–18%), with rates varying from 6.8% to 23.8% across the different atolls.³⁰ The rates for α-thalassaemia and HbE were estimated at 2% and 1%, respectively. As a result, 1 in 120 live births is affected by a thalassaemia major. Data suggest that there are between 10 and 15 new TDT cases per year in Maldives.

The frequencies of α-thalassaemia, β-thalassaemia and HbE in Myanmar are estimated at 10.5%, 4% and 1–26%, respectively. α-thalassaemia ranges from 10% to 14% in the Bamar (Central region) to more than 34% in the Kachin (North) and Shan (East) populations. β-thalassaemia trait varies from 0.54% (Bamar) to 6.7% (Kayin), with frequencies of 1–3% observed in the Kachin, Kayah, Chin, Mon, Rakhine and Shan. The prevalence of HbE was 1% in the Kayin (South-eastern region), 28% in the Bamar and >70% in the Chin and Rakhine (Western and North-western regions). The annual number of new births affected by thalassaemia in Myanmar was estimated to 250 for homozygous β-thalassaemia and 260 for HbE-thalassaemia.⁵³ A more recent analysis suggested 52–155 β-thalassaemia major (β⁰/β⁰); 18,700–135,000 HbE β-thalassaemia intermedia; 1030–1670 Hb Barts Hydrops fetalis; and 21,000–28,000 HbH per year (Win, pers. com.). These estimates for severe forms of α-thalassaemia are much higher than in any of the other countries in the region and are likely to be substantial overestimates.

Limited prevalence data are available for Nepal. A small study (n = 439) in the lowland regions of the country found a frequency of α+-thalassaemia ranging from 4.8% in the Tamang to 56.9% in the Danuwar. HbE was only identified in this latter subgroup. A study of 1200 individuals in the Southeast of Nepal identified 4.1% of β-thalassaemia trait and 2.8% of HbE.⁵⁴ An HbE prevalence of 19% was found in a study of 300 randomly selected individuals in a central area of Nepal.⁵⁵ A large multi-site study of 4018 individuals suggested substantial variations in Central Nepal, with β-thalassaemia frequency varying from 0.0% in the Bharatpur Hospital, Chitwan to 20.5% in the National Public Health Laboratory, Kathmandu.⁵⁶ A total of 225 thalassaemia patients, mostly TDT and primarily from the Terai area and Tharu community, are registered with the Nepal Thalassemia Society. In a hospital-based study of 187 TDT patients in a tertiary paediatric hospital, β-thalassaemia major was found in 156 (83.4%), HbE/β-thalassaemia in 22 (11.8%), HbH disease in 5 (2.7%), and β-thalassaemia intermedia in 4 (2.1%) patients.⁵⁷

The national carrier frequency of β-thalassaemia in Sri Lanka is estimated at 2–3%, while HbE has a carrier prevalence of around 0.5%.^7,47 α-thalassaemia trait is relatively common (∼9.9%), largely driven by α⁺ deletions. Epidemiological surveys from Sri Lanka indicate that nearly 2000 thalassaemia patients live with a clinically significant disease, of which 68.7% had homozygous β-thalassaemia, 20.3% HbE β-thalassaemia, and 2.0% sickle β-thalassaemia. The remaining 9.0% included patients with β-thalassaemia intermedia, β-thalassaemia trait, δβ-thalassaemia or an uncertain diagnosis. HbH is quite rare in Sri Lanka, with fewer than 20 patients identified so far. About 45–55 affected births are occurring annually, with limited temporal change over the last two decades.⁵⁸

In Thailand, the carrier frequencies of α-thalassaemia and β-thalassaemia have been estimated at 20–30% and 3–9%, respectively. HbE and HbCS are prevalent in 10–53% and 1–8% of the population. It has been estimated that approximately 98,460 individuals are affected by the three major severe thalassaemia syndromes: Hb Bart's hydrops fetalis, homozygous β-thalassaemia, and HbE/β-thalassaemia disease. This number increases to approximately 434,460 cases when HbH disease is included. Around 17,012 couples are identified annually as being at high risk of having children with severe thalassaemia, resulting in an estimated 4253 newborns with severe thalassaemia syndromes each year. Because of the national screening and prevention programmes implemented in Thailand, between 83.7% and 99.8% of pregnant women attending antenatal care receive thalassaemia screening, and 34.6–100% of women confirmed to carry a foetus affected by a severe thalassaemia choose to terminate the pregnancy, which has contributed to substantially reducing the number of births affected across Thailand.⁵⁹

Because of the general lack, at least in the published literature, of repeated data on the prevalence (or incidence) of the thalassaemia syndromes in the SEAR, it is difficult to assess temporal trends in the burden of the conditions.

Mortality

There are very limited data on thalassaemia survival and mortality across the SEAR. Hossain and colleagues wrote in 2017 that virtually nothing was known about the morbidity and mortality of thalassaemia in Bangladesh.²⁷

In India, mortality associated with β-thalassaemia major is considered to remain high despite advances in the management of these syndromes. In a retrospective analysis (2011–2018) of 1087 β-thalassaemia patients from five centres across southern India, the median age of the patients was 8.5 years with only 107 patients being over 18 years of age. There was a male preponderance (males: 656, females: 431). The clinical parameters were assessed at presentation and during the last follow up. There were 41 recorded deaths with the average age at death being 15.4 years and survival at 26.9 years being 50%. The under-five mortality in this study was substantially higher than in the general population. The main causes of death were infection, iron-overload, transfusion transmitted infections and alloimmunization.⁶⁰ Although the number of adults with thalassaemia in India is increasing, mortality in TDT patients in many parts of the country continues to be a challenge.

Thalassaemia in Maldives has historically been a major contributor to childhood mortality. Advances in regular transfusion protocols and supportive care have significantly improved survival, allowing many patients to reach adolescence and early adulthood. Nevertheless, data from Maldives Blood Service show that not many individuals survive beyond their 30s (Saleem, pers. com.). About five deaths per year are attributed to thalassaemia syndromes.

In Sri Lanka, the median survival in a cohort of 109 patients with HbE β-thalassaemia was estimated at 49 years (95% CI: 45–not reached).⁶¹ Despite free healthcare (including blood transfusions and iron chelation) being provided by the state, the overall survival of patients of β-thalassaemia major is still considered to be lower than in Mediterranean countries.⁴⁷

In a study of 789 α-thalassaemia and β-thalassaemia patients in northern Thailand, the average age at death of 65 deceased individuals (8.2%) was 17.0 ± 0.9 years.⁶² Nevertheless, in a 10 years longitudinal study of 380 TDT patients in north-eastern Thailand, the median age at death was 45 years (range: 22–72).⁶³ An analysis of nationwide healthcare databases covering 96,289 admissions for thalassaemia identified 708 deaths per year, with the mortality rate increasing exponentially after 40 years of age (from 1 per 100,000 among those aged 31–40 years to 4.4 per 100,000 among those aged >80 years).

Because of overall reductions in under-five mortality and increasing life expectancy, thalassaemia patients are likely to survive longer in most parts of the SEAR. As a result, the number of individuals requiring lifelong treatments, such as regular blood transfusions and iron chelation, and the pressure that they exert on the healthcare systems are increasing.

Prevention

Prevention strategies vary considerably in scale and effectiveness across the SEAR. Sri Lanka has operated a national voluntary screening and “safe marriage” counselling programme for over 15 years. Yet, no meaningful reduction in incidence has been observed, partly because pregnancy termination remains illegal.⁵⁸ India has implemented screening programmes through multiple national initiatives, but coverage is uneven, methodologies are inconsistent, and formal evaluations are limited.²² Myanmar has no national thalassaemia registry, no national guidelines, and no prenatal diagnosis or genetic counselling programme.³³ Pregnancy termination is culturally and religiously unfavourable, severely limiting prevention options. Although thalassaemia has been recognised as a public health problem at policy level in Bangladesh, there is currently no national policy or guideline on thalassaemia screening or prevention, no national thalassaemia registry, no national diagnostic, or prenatal or genetic counselling programme.²³

In Nepal, thalassaemia prevention remains at an early stage and is largely limited to opportunistic rather than population-based screening and does not have a national thalassaemia prevention programme, a nationwide carrier screening strategy, or a national registry to guide policy and resource allocation.²⁴ Genetic counselling services are also limited and are not routinely integrated into maternal and child health services. In contrast, Maldives have the most developed legislative framework, with a national registry and a national screening programme established since the early 1990s, a Thalassaemia Law enacted in 2012 and a National Thalassaemia Action Plan released in 2024.³⁰ However, the registry requires digitisation and improved data disaggregation, and premarital screening programmes need expanding.

Thailand established a nationwide thalassaemia prevention and control programme in 1992. To further strengthen disease prevention efforts, the National Thalassemia Action Plan (2007–2011) was introduced with the dual objectives of reducing the incidence of severe thalassaemia among newborns and improving the quality of life of affected patients. Subsequently, the National Health Security Office (NHSO) launched the Thalassemia Prevention and Control in Pregnancy Program during 2014–2016, integrating thalassaemia screening and prenatal diagnostic services into routine antenatal care. The programme in Thailand is considered to be successful in preventing and controlling thalassaemia, but migration represents an important concern.⁶⁴ Progress, challenges and future directions for the prevention of thalassaemia in Southeast Asia are discussed more in detail by Angastiniotis and colleagues.⁶⁵

Challenges

As reflected by the evidence compiled above, most of the SEAR countries lack national-level policies for the identification and management of the thalassaemia syndromes, which are essential to drive substantial improvements in morbidity, mortality and quality of life, and to ensure sustainable healthcare provision. The SEAR countries face particular challenges due to the high prevalence of specific severe forms of thalassaemia in the region, such as HbE β-thalassaemia. Other challenges include high consanguinity, poor availability of safe blood, the economic burden, gender disparities and population movements across the region. Each of these challenges is covered briefly below.

Consanguinity

The prevalence of severe forms of thalassaemia can be exacerbated by consanguinity, a cultural practice of inbreeding common in most regions of the world where haemoglobinopathies are endemic, including the SEAR. A large-scale survey (n = 3694 families) reports that the prevalence of consanguinity ranged from 3.1% (rural Khulna) to 9.5% (rural Sylhet) in different regions of Bangladesh.⁶⁶ In India, when the National Family Health Survey (NFHS) analysed the data for 456,646 married women between the ages of 15 and 49 years, the prevalence of consanguineous marriages was 9.9%, being highest in the South (23.0%) and lowest in the North-Eastern region (3.1%).⁶⁷ In a hospital-based study of 187 TDT cases in Kathmandu (Nepal), consanguinity was reported in 1.1%.⁵⁷ Better education about the inheritance of the thalassaemia syndromes and accounting for carrier status in often arranged marriages may contribute to the prevention of severe disorders.

Blood availability

Regular blood transfusion is a requisite for the effective management of severe thalassaemia and of some thalassaemia intermedia. Patient adherence can be high (e.g. from 55% to 90% in Maldives).^68,69 Nevertheless, as in many other parts of the world, blood availability is an important limitation in most SEAR countries.^12,70 When blood transfusions are available, there can be issues of treatment continuity and costs.

A hospital-based study in Bangladesh showed that nearly 80% of patients experienced difficulties in securing regular blood donors, while approximately 81% received no assistance from organised blood donation groups.⁷¹ In Nepal, 72% (n = 39) of patients in the capital city had to interrupt regular blood transfusion due to the unavailability of packed red blood cells.²⁴ In a nationwide survey of 67 transfusion centres across India, 26% reported donor scarcity as a challenge.⁷² Simulations suggested that 43% of the 11.1 million units of blood collected in 2016–2017 in India would have been used to meet the transfusion requirements of children with a haemoglobinopathy if they were all being adequately treated. The projected annual blood requirements of thalassaemia patients over 10 years (2017–2026) showed that there would be an increase in blood units from 4.5 million to 8.25 million.⁷³ In Maldives, sustaining a reliable blood supply remains a critical challenge for TDT patients. Key constraints include periodic blood shortages, low voluntary blood donation rates (estimated at 10–30%), and limited national coordination between blood banks. A public awareness programme in Myanmar has successfully increased the proportion of voluntary non-remunerated donors between 2000 and 2006.⁷⁴

Economic burden

In Bangladesh, the financial burden for thalassaemia patients is high as out-of-pocket expenditures account for 74% of healthcare costs, substantially higher than the 45–55% reported in India, Pakistan, Nepal, and Sri Lanka.⁴⁸ A recent analysis of data from 67 governmental, private and charitable transfusion centres in India estimated the monthly out-of-pocket costs to range from 500 INR to 16,000 INR (5.9–189.5 USD) even when free transfusions and chelation were available.⁷² In Myanmar, the financial burden of transfusion visits was estimated to represent about 10–40% of the total monthly family income (Win, Pers. Com.). The average annual cost of thalassaemia care, including blood transfusion, commute to the transfusion centre, and iron-chelating agents, in Nepal is high: 70,000 NRS (∼533 USD) in paediatric patients and 250,000 NRS (∼1906 USD) in adult patients.²⁴

Gender disparities

Important gender inequalities, affecting both physical and mental health, remain across the SEAR. A striking treatment-seeking gender bias has been documented in India with 64–73% of patients receiving care being male, which reflects preferential investment in sons.⁷⁵ The same study reported a 2.4:1 male-to-female ratio in the 10–20 age group receiving treatment.⁷⁵ Similarly, a study from Nepal found that 65% of TDT patients receiving care in a paediatric tertiary hospital were male, highlighting the disparities in access to care.⁵⁷ In Sri Lanka, caregiving responsibilities fall predominantly on mothers, who often withdraw from employment to manage lifelong transfusion and chelation schedules.⁷⁶ Nevertheless, a study of 125 thalassaemia children in Chennai, India, did not find a difference in health-related quality of life between male and female children.⁷⁷

Evidence also indicates important gaps in knowledge and outcomes related to growth and pubertal development among individuals with thalassaemia. Females living with thalassaemia in Maldives may face barriers to accessing timely and comprehensive health services, including sexual and reproductive health care.⁶⁶ Delayed puberty (onset 14–16 years) is common and poorly monitored, highlighting the importance of routine monitoring and specialised follow-up in females.⁶⁶ Strengthening the integration of sexual and reproductive health services within thalassaemia care pathways may help address unmet needs, improve health outcomes and reduce gender inequalities.⁷⁸ Social and cultural expectations related to fertility and childbearing disproportionately affect women. Although both males and females are affected by reproductive health complications, the burden is disproportionately experienced by females.⁷⁹ Anecdotal evidence suggests that many females face significant social consequences, including stigma, exclusion, and psychological distress, particularly in relation to infertility or delayed childbearing.80, 81, 82

Specific issues in relating to folic acid supplementation in pregnant women and adolescent girls may also need to be considered in the management of thalassaemia across the SEAR.⁸³

Finally, in Bangladesh, the proportion of thalassaemia patients aged 2–60 years old reporting good mental health was lower in female (16.0%) than in male (19.1%).⁸⁴ Another study, also conducted in Bangladesh, found that a high proportion of mothers of thalassaemia patients experienced stress (62%), anxiety (58%) or depression (63%).⁸⁵

Across all settings, addressing gender disparities, both in access to care and in the burden borne by female caregivers, has been identified as essential to improving outcomes.

Migration

Countries in the SEAR face increasing migration, from labour migrants crossing national borders to forced migration due to conflicts, environmental displacement or refugee flows. These migratory flows influence the distribution of the thalassaemia syndromes across the region.

Although haemoglobinopathies tended to be confined to specific parts of the SEAR countries, their distribution has expanded. Large population movements following the partition of India in 1947 and various conflicts introduced high-frequency mutations, such as IVS-I-5(G > C), into the Northern and Western parts of the country.⁸⁶ There is a considerable genetic heterogeneity in thalassaemia in Nepal due to its geographical location between the Indian subcontinent and the Tibetan-Himalayan region.³⁴ There is marked variation in β-globin mutations among different ethnic populations, which closely resembles that of northern India and parts of Myanmar, reflecting historical migration and admixture across South Asia.³⁴

More recently, migrations from rural areas to major cities have created more complex, mixed mutation profiles, as well as issues relating to awareness and stigmatisation. A nationwide study of randomly selected participants across Bangladesh found an almost twofold disparity in thalassaemia awareness (65.1% in urban residents compared to 38.2% in semi-urban and rural residents).⁸⁷ In Sri Lanka, internal rural-to-urban migration has redistributed patients towards the Western Province, placing strain on urban services.⁸⁸ Contemporary labour migration is beginning to introduce new haemoglobin variants, with implications for future screening programmes. In Thailand, migrant populations do not tend to benefit from screening and diagnosis programmes in place. Awareness of thalassaemia was estimated at 4% in migrants compared to 80% in the Thai population.⁶⁴ Providing thalassaemia education tailored to migrant audiences in both clinical and community settings; adopting carrier screening as part of a prevention strategy; and eliminating structural barriers, by providing universal coverage for screening and preventive care for migrants, engaging employers, conducting thalassaemia screening in convenient locations, increasing the availability of interpreters in medical facilities, and providing healthcare workers with cultural competency training, are some of the strategies proposed to support migrant communities.

Finally, global migrations from the region also led to many cases of thalassaemia seen in North America, Europe and the Middle East,¹³ where thalassaemia patients can benefit from high standards of care, but specific awareness and education need to be tailored to the social, cultural and religious characteristics of sub-populations.⁸⁹

Knowledge gaps and recommendations

Detailed spatial and temporal epidemiological data not only allow us to define present healthcare needs, but also to make projections for the future and to define the best strategies to meet the challenges identified and the objectives set. Recent improvements in haploidentical haematopoietic stem cell transplantation, combined with the rapid emergence of large-scale clinical trial capacity, particularly in India and Chinas),^90,91 have substantially increased the global accessibility of such curative options. In parallel, we have seen extremely rapid developments of gene therapies for thalassaemia, which offer promising, albeit very expensive, alternative curative options. Nevertheless, it is unlikely that most patients across the SEAR will benefit from these advances in the short-term. There remain important gaps in our knowledge of the prevalence, incidence and mortality of thalassaemia across parts of the SEAR, particularly as migrations influence the distribution of the syndromes. The total lack of published evidence on the epidemiology of thalassaemia from Bhutan, the Democratic People Republic of Korea and Timor-Leste was particularly striking.

Digitising healthcare systems and establishing national registries of patients would enable routine collection and analysis of epidemiological data for policy and research. International efforts, such as RADeep in Europe, to standardise the information collected may provide valuable insights for SEAR countries. Networking and collaborations (including South-South),⁹² such as the Thalassaemia International Federation (TIF) and the Asian Thalassaemia Network set up in 2005, are essential for knowledge exchange, capacity building, and harmonisation of best practices in thalassaemia prevention and care.

Based on decades of evidence from different countries around the world, including Cyprus and Iran, the most effective programmes to reduce the long-term burden of haemoglobinopathies are those based on the prevention of affected births through premarital testing, prenatal diagnosis and genetic counselling. Thailand is probably the SEAR country in which the clearest signs of success have been observed in recent decades.

The management of current cohorts of patients with thalassaemia largely relies on blood transfusion and iron chelation. This is essential for TDT patients, but also for NTDT individuals who may occasionally require a blood transfusion. More donations are required, but better coordination of blood supplies and demands across and between SEAR countries would likely contribute to addressing current and future needs.

National guidelines, such as those produced in 2016 by the Indian Ministry of Health and Family Welfare⁹³ or in 2023 by the Indian Academy of Pediatrics, with a revision in 2026,⁹⁴ can also help tailor international guidelines^5,6 to specific contexts.

As most SEAR countries face significant economic challenges and uncertainties, cost-effectiveness analyses, performed in collaboration with health economists, may provide the evidence required to influence local policies and prioritise interventions for the prevention and management of the thalassaemia syndromes.

Education and awareness of the thalassaemia syndromes amongst the general public, but also amongst healthcare professionals is another important gap across the region. Advances in artificial intelligence may potentially help circulate socially, culturally and religiously sensitive information translated into a vast array of local languages and dialects. Patient societies, such as the Nepal Thalassaemia Society or the Thalassaemia Foundation of Thailand, can play major roles in this area.

Conclusions

The thalassaemia syndromes remain a significant and largely unmet public health challenge across the SEAR. Despite the availability of effective preventive strategies and improving therapeutic options, the majority of affected populations continue to face inadequate screening, limited access to safe blood and high-quality treatment options, and insufficient policy support. Closing the epidemiological knowledge gaps through digitised registries, standardised data collection, and sustained international collaboration is essential to inform effective, context-sensitive interventions. Without renewed political commitment and equitable resource allocation, the human and economic toll of thalassaemia across the SEAR will continue to grow.

Contributors

F.B.P. conceived the study, reviewed the data and wrote the first draft. All other authors collated and analysed local data and contributed their expertise. All authors reviewed, edited and approved the final manuscript.

Data sharing statement

All the data presented in this review came from published sources or personal communications with experts in the countries studied.

Declaration of interests

None of the authors has a conflict of interest to declare.