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Severe thalassemia diseases are a major health problem in Southeast Asia. In Cambodia, there has never been a significant program for prevention or control of severe thalassemia. We, therefore, studied the effect of a health education program on severe thalassemia prevention and control in Phnom Penh, Cambodia. A quasi-experimental study in several communities around Phnom Penh was done. The respective intervention and control group comprised 124 and 117 people, between 18 and 40 years of age, male and female. Pre- and post-tests using a validated and reliable questionnaire were performed in the intervention group and one test was done in the control group. A health education program was organized to give important information to the intervention group and, at the end of the process, to the control group. The outcomes were evaluations of their knowledge and attitude vis-à-vis severe thalassemia prevention and control, and participating in thalassemia screening. Among participants in the intervention group, 105 (84.7%) considered undergoing blood screening vs. 65 (55.6%) in the control group (p-value < 0.001). In the intervention group, the respective mean scores for knowledge and attitude to a prevention and control program for severe thalassemia before and after health education were 2.6 VS 6.5 (p-value < 0.001) and 4.6 VS 6.5 (p-value < 0.001). The intention to undergo screening was significantly higher in the intervention group than the control group. Knowledge and attitude towards prevention and control of severe thalassemia was significantly improved in the intervention group. Health education clearly heightens awareness and improves consideration of screening for prevention and control of severe thalassemia.

α0-thalassemia of SEA deletion (—SEA) is common among Southeast Asian and Chinese. Using haplotype and phylogenetic analyses, we examined the origin of this defect in Southeast Asian populations. Study was done on both normal and α0-thalassemia alleles in 3 ethnic groups including 96 Thai, 52 Laotian and 21 Cambodian. Five SNPs encompassing the (—SEA) including (rs3760053 T>G), (rs1211375 A>C), (rs3918352 A>G), (rs1203974 A>G) and (rs11248914 C>T) were examined using high-resolution melting assays. It was found that 94.0% of Thai, 100% of Laotian and 100% of Cambodian α0-thalassemia alleles were linked to the same haplotype: the haplotype H4 (AAGC), representing an Asian specific origin. An G allele of the (rs3760053) was found to be in strong linkage disequilibrium with the α0-thalassemia allele in these populations. A multiplex PCR assay was developed to detect simultaneously the (—SEA) allele and genotyping of a linked (rs3760053) to improve accuracy of prenatal diagnosis of α0-thalassemia. Application of this multiplex PCR assay for routine prenatal diagnosis of α0-thalassemia in 12 families revealed a 100% concordant result with conventional gap-PCR assay. Therefore, a single genetic origin is responsible for the spread and high prevalence of the (—SEA) in the region. The multiplex PCR assay developed should provide a double-check PCR system for more accurate diagnosis and allow the monitoring of possible maternal contamination at prenatal diagnosis of this important genetic disorder.

Primary screening for thalassemia and hemoglobinopathies usually involves an accurate blood count using an expensive electronic blood cell counter A cheaper alternative method was tested by using a modified osmotic fragility (OF) test and a modified dichlorophenolindophenol (DCIP) test. Altogether 423 pregnant Thai women participated in this project. Hemoglobin patterns and globin genotypes were determined using an automated high-performance liquid chromatography analyzer and polymerase chain reaction analysis of alpha- and beta-globin genes. Among the 423 subjects, 264 (62.4%) carried thalassemia genes. The combined OF and DCIP tests detected all pregnant carriers of the 3 clinically important thalassemias, ie, alpha0-thalassemia, beta-thalassemia, and hemoglobin E with a sensitivity of 100.0%, specificity of 87.1%, positive predictive value of 84.5%, and negative predictive value of 100.0%, which show more effectiveness than these values for the standard method based on RBC counts. A combination of modified OF and DCIP tests should prove useful and applicable to prenatal screening programs for thalassemia and hemoglobinopathies in communities with limited facilities and economic resources.

AimsThe presence of the ζ-globin chain is a good marker of (--SEA) α0-thalassaemia. We evaluated an immunochromatographic (IC) strip assay for ζ-globin in screening for (--SEA) α0-thalassaemia in a population with a high prevalence and heterogeneity of haemoglobinopathies.MethodsThe study was carried out on 300 screen positive blood samples of Thai individuals. The IC strip assay for the ζ-globin chain was performed on all samples. The results were interpreted with thalassaemia genotyping using standard haemoglobin and DNA analyses.ResultsSeveral thalassaemia genotypes were noted. Among the 300 subjects investigated, 79 had a positive IC strip assay for ζ-globin and (--SEA) α0-thalassaemia was identified in 40 of them. No (--SEA) α0-thalassaemia was detected in the remaining 39 samples with a positive IC strip test result or in the 221 samples with a negative IC strip test result. Further DNA analysis identified α+-thalassaemia in 25 of the 39 (--SEA) α0-thalassaemia negative samples. Using this IC strip assay in combination with a conventional screening protocol for (--SEA) α0-thalassaemia could provide sensitivity and specificity of 100% and 90.4%, respectively.ConclusionsIC strip assay for ζ-globin is simple, rapid and does not require sophisticated equipment. Use of this test in addition to the existing screening protocol could detect potential (--SEA) α0-thalassaemia leading to a significant reduction in the workload of DNA analysis. This could be used in areas where haemoglobinopathies are prevalent and heterogeneous but molecular testing is not available.

AbstractIn a distal renal tubular acidosis, a patient with coexistence of anion exchanger 1 (AE1) mutation and α-thalassemia had more severe clinical phenotype than usually observed. AE1 mutation might therefore modify the hematological and clinical presentations of the hemoglobin (Hb) E-β-thalassemia disease. To examine the role of AE1 mutation on severity difference in Hb E-β-thalassemia disease in northeast Thailand, three common AE1 mutations were investigated in Hb E-β-thalassemia patients with thalassemia major (TM) and thalassemia intermedia (TI) phenotypes. One hundred forty-eight patients including 103 TM and 45 TI were studied. Three common AE1 mutations including Southeast Asian Ovalocytosis (SAO), G701D and A858D were screened for using allele specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) assays. No any AE1 mutation was detected in all these Thai patients with Hb E-β-thalassemia. This result indicates that AE1 mutation is rare and should not be an important phenotypic modifier in the Hb E-β-thalassemia disease. Therefore, screening of common AE1 mutation in thalassemia patient is not necessary.

Globin chain imbalance and tissue hypoxia are important determinants of the clinical severity of thalassemias. Phenotypic expression may be further modified by interactions between α- and β-thalassemia defects. We retrospectively and prospectively studied the clinical and hematologic features in children and adults with hemoglobin (Hb) E traitHb H disease (SEAPaksé) (seven cases) and Hb E traitHb H disease (SEAConstant Spring) (29 cases) and found that they had similar presentations. The severity of these two intermediate thalassemic manifestations ranged from very mild to severe. Severe anemia developed in accordance with very high fever, whereupon the range of Hb and hematocrit (Hct) levels declined to 5.2–5.8 gdL and 13–19, respectively. In one case, during a hemoconcentrated state as occurs in dengue hemorrhagic fever, the Hb and Hct were 10 gdL and 31; the latter rose to 35 after fluid therapy. In some patients, the range of Hb and Hct levels was constantly low (4.3–5.8 gdL and 15–19, respectively). (If dengue hemorrhagic fever is misdiagnosed, a fatal outcome may occur for thalassemic patients.) After a hemodiluted condition as in acute post-streptococcal glomerulonephritis, the respective Hb and Hct were 5.4 gdL and 19. These observations suggest that the instability of Hb E, especially during fever, may play an important role in the clinical manifestations of Hb E traitHb H disease with Hb Paksé and with Hb Constant Spring.

AbstractThe frequencies of hemoglobin E and βE-globin gene haplotypes were determined in eight minority groups living in the northeastern part of Thailand. A total of 478 samples of eight minority groups, namely Soui, Thai Khmer, So, Yor, Phuthai, Thai Puan, Thai Loei and Thai Dam, were examined. High prevalences of hemoglobin E (>50%) were observed in Soui, Thai Khmer, So, Yor and Phuthai inhabiting the region near Cambodia and Laos. Thai Puan, Thai Loei, Thai Dam and native Thai living in the same geographical area had prevalences of 42.6, 35.9, 21.4 and 27.9%, respectively. A prevalence of 9.5% was found among the Thai with Chinese background living in the same area. β-Globin gene haplotypes analysis demonstrated that most of the βE-globin genes in these Thai populations were associated with two haplotypes: (– + – + + + –) and (+ – – – – + –) on chromosomes with framework 2 variety. Some βE-globin genes in Soui and Thai Khmer groups were associated with the framework 3 chromosome. Genetic distances based on the β-globin gene haplotypes between minority groups revealed that Soui and Thai Khmer were closely related to each other. This finding has a valuable implication for study of the origin and spread of hemoglobin E in the region.Copyright © 2002 S. Karger AG, Basel