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Background and objectives: Haemoglobin E β-thalassaemia has a variable clinical presentation. This study describes the clinical spectrum of these patients in two thalassaemia centers in Malaysia in addition to determining the prevalence of selected primary and secondary genetic modifiers which may influence its phenotype. Methods: A total of 99 patients were recruited in this cross-sectional study. Clinical parameters and severity scoring were determined. Molecular analysis was performed: Sanger sequencing and MLPA for β globin mutations; multiplex PCR for α-globin gene deletions and RFLP-PCR for XmnI polymorphism.Results: Patients with mild HbE β-thalassaemia were diagnosed at a later age as compared to the severe group (mean 3.14 and 1.6 years, p = 0.03). Haemoglobin level at diagnosis was higher for the mild group as compared to severe group (7.9 g/dL ± 1.97 and 6.0 g/dL ± 1.00, p = 0.02). The commonest β mutation in Malays were IVS1-5 (51.69%) and CD41/42 (20.2%) whereas in the Chinese, IVS2-654(44.4%) and CD41/42(33.4%). Single α-gene deletion (-α3.7/αα) was found in 4% of patients and none were homozygous for XmnI (+/+) polymorphism. Conclusion: Age at presentation and haemoglobin level at initial diagnosis is useful as clinical predictors of disease severity. The majority of our patients had β° gene mutation i.e. IVS1-5 and CD41/42, which accounted for the moderate to severe phenotype based on clinical severity scoring.

The risk of contact infection among susceptible individuals in a randomly mixed population can be reduced by the presence of immune individuals and this principle forms the fundamental of herd immunity. The conventional susceptible-infectious-recovered (SIR) model features an infection-induced herd immunity model, but does not include the reducing risk of contact infection among susceptible individuals in the transmission model, therefore tends to overestimate the transmission dynamics of infectious diseases. Here we show that the reducing risk of contact infection among susceptible individuals can be achieved by incorporating the proportion of susceptible individuals (model A) or the inverse of proportion of recovered individuals (model B) in the force of infection of the SIR model. We numerically simulated the conventional SIR model and both new SIR models A and B under the exact condition with a basic reproduction number of 3·0. Prior to the numerical simulation, the threshold for the eradication of infectious disease through herd immunity was expected to be 0·667 (66·7%) for all three models. All three models performed likewise at the initial stage of disease transmission. In the conventional SIR model, the infectious disease subsided when 94·0 % of the population had been infected and recovered, way above the expected threshold for eradication and control of the infectious disease. Both models A and B simulated the infectious disease to diminish when 66·7% and 75·6% of the population had been infected, showing herd immunity might protect more susceptible individuals from the infectious disease as compared to the projection generated by the conventional SIR. Our study shows that model A provides a better framework for modelling herd immunity through vaccination, while model B provides a better framework for modelling herd immunity through infection. Both models overcome the insufficiency of the conventional SIR model in attaining the effect of herd immunity in modelling outputs, which is important and relevant for modelling infectious disease, such as the COVID-19 in a randomly mixed population.