Thalassemia in the United Arab Emirates: Why it can be prevented but not eradicated

Abstract

Thalassemia is a genetic blood disorder that causes abnormal hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen and is made of two proteins from four α-globin genes and two β-globin genes. A defect in one or more of these genes causes thalassemia. The treatment of thalassemia mostly depends on life-long blood transfusions and removal of excessive iron from the blood stream. Such tremendous blood consumption puts pressure on the national blood stock in many countries. In particular, in the United Arab Emirates (UAE), various forms of thalassemia prevention have been used and hence, the substantial reduction of the thalassemia major population has been achieved. However, the thalassemia carrier population still remains high, which leads to the potential increase in the thalassemia major population through carrier-carrier marriages. In this work, we investigate the long-term impact and efficacy of thalassemia prevention measures via mathematical modeling at a population level. To our best knowledge, this type of assessment has not been done before and there is no mathematical model that has investigated such a problem for thalassemia or any blood disorders at a population level. By using UAE data, we perform numerical simulations of our model and conduct sensitivity analysis of parameter values to see which parameter values affect most the dynamics of our model. We discover that the prevention measures can contribute to reduce the prevalence of the disease only in the short term but not eradicate the disease in the long term.

Fig 1. Schema of population dynamics of the mathematical model.

Each box represents a population subgroup, i.e. compartment. The arrows indicate how the population in each compartment could move from one compartment to another via our mathematical model. The variable names are found in Table 2 and the mathematical equations on the arrows can be found in S1 Material. For example, b_K U means newborn boys or girls from married coupled and hence they are moved to the children compartments G_M or G_F.

Fig 2. Simulation results of thalassemia major population in both genders with different level of marriage reconsideration rates.

(a) Thalassemia female T_F with different marriage reconsideration rates. (b) Thalassemia male T_M with different marriage reconsideration rates. ν_K and ${\tilde{\nu }}_K$ are the marriage reconsideration rates of educated and uneducated carrier populations for K = {M, F}. ν_K = 0 ($\widetilde{{\nu }_K}=0$) means all of uneducated (educated) carrier males or females do not give up their marriage decision, whereas ν_K = 1 ($\widetilde{{\nu }_K}=1$) means all of uneducated (educated) carrier males or females do give up their marriage decision due to screening and education. The education and premarital screening rates are as in Table 3.

Fig 3. Sensitivity regarding the birth, death, thalassemia diagnosis rates with respect to thalassemia populations.

(a) Sensitivity of b_F, ${\eta }_T^F,$ $d_G^F,$ d_T and d_F with respect to T_F. (b) Sensitivity of b_M, ${\eta }_T^M,$ $d_G^M,$ d_T and d_M with respect to T_M. Note that b_M, b_F are birth rates, $d_G^M,$ $d_G^F$ are child mortality rates, d_M, d_F and d_T are normal male and female death rates and thalassemia induced death rates, respectively.

Fig 4. Sensitivity regarding the education, marriage reconsideration and premarital screening rates with respect to thalassemia major population in both genders.

(a) Sensitivity of ϵ, ν_F, ${\tilde{\nu }}_F,$ and ${\alpha }_s^F$ with respect to T_F. (b) Sensitivity of ϵ, ν_M, ${\tilde{\nu }}_M,$ and ${\alpha }_s^M$ with respect to T_M. Note that ε is the education rate, ν_K and ${\tilde{\nu }}_K$ the marriage reconsideration rates of uneducated and educated carrier populations, respectively, and ${\alpha }_s^K$ is the premarital screening rate. The inner plots in (a) and (b) are the enlargement of sensitivity regarding ϵ, ν_K, and ${\tilde{\nu }}_K,$ where K = {M, F}.

Fig 5. Sensitivity regarding premarital screening rates with respect to educated and uneducated carrier populations.

(a) Sensitivity with respect to uneducated and educated carrier single males, $C_M^A$ and $C_M^{AE}.$ (b) Sensitivity with respect to uneducated and educated carrier single females, $C_F^A$ and $C_F^{AE}.$ Note that ${\alpha }_s^M$ and ${\alpha }_s^F$ are the premarital screening rates for males and females who are about to marry.