The inherited disorders of hemoglobin (Hb), mainly sickle cell disease (SCD) and thalassemia, are the most common and worldwide distributed monogenic disorders. Around 7% of the world’s populations were assumed to be carriers of a significant hemoglobinopathy mutation [1]. In Sub-Saharan Africa, SCD affects up to 2% of newborns and the prevalence of sickle cell trait (SCT) reaches 40% in some areas [2].

SCD constitutes a group of autosomal recessive β-globin abnormalities with the hemoglobin S-variant (HbS) as a common pathognomonic feature. The anomaly can occur homozygously (βS/βS) leading to the homozygote phenotype HbSS or as a compound heterozygous state (βS/βX) combining the basic mutation βS on one allele with the other allele, one of a number of another abnormal β-globin allele (βX) giving the composite heterozygous phenotypes HbSC, Sβ0- or Sβ+-Thalassemia, SD-Punjab, SO-Arab, etc.) [3] [4].

In SSA, deaths due to SCD mostly occur in children under five years old [3] [5]. Therefore, the WHO declared SCD a global health priority and urged each country to set up a national comprehensive control program [2]. Many studies indicate that effective strategies that contribute significantly to the reduction of morbidity and mortality include, among others, the early diagnosis and treatment of affected subjects through neonatal screening (prevention of 70% of deaths). However, few countries in SSA have such SCD programs. Sometimes, reliable data to support the development of a relevant program is lacking.

In Burkina Faso, the hospital prevalence of all hemoglobinopathies and SCD varied between 44.8% - 41.2% and 8.4% - 12.1% respectively [6] [7], accounting for more than 60% of non-malignant hematological pathology [8]. Among children over two years of age and adolescents in a community study, their prevalence was found to be at 30% and 1.4% respectively [6]. These data are quite partial and concentrated on the city of Ouagadougou and its surroundings. The first study on neonatal screening was conducted sequentially between 2000 and 2004 in the peripheral maternities of Ouagadougou. It is the only one that has made available the most complete and reliable data on hemoglobinopathies that the country has ever known. Abnormal hemoglobin was found in 27.4% of newborns and SCD occurred in one out of 57 newborns [9].

In this work, we report data from a somewhat larger study on SCD and other significant hemoglobinopathies that may be useful for policy decisions.

Over the 5-years study period, a total of 11,343 newborn samples were tested. Six (0.05%) were excluded for the inconclusive profile (Figure 1). Males accounted for 47.8%. The majority of samples (60.2%) were from Bobo-Dioulasso. In the first year (2015), all samples were from Ouagadougou. 2/3 of the samples were tested during the first three years (Table 1). As shown in Table 1, at least an abnormal Hb fraction was found in 3076 samples; i.e., 27.1% representing a cumulative incidence of 1:4 newborns, with a relative increase in frequency from

n, number; %, percentage; Hb, Hemoglobin; SCD, sickle cell disease; Cβ-Thal, Cβ-Thalassemia.

year to year (Kh² = 29.96; p< 0.0001). Among them, SCD was found in 1.9% of all samples (cumulative incidence of 1:53) with homozygotes SS cases which accounted for 27.9% (Table 1). Hemoglobinopathies C (HbCC and Hb Cβ-Thalassemia) accounted for 1.1% (Table 1), representing and cumulative incidence of 1:90 newborns.

The incidence of SCD was 1.51 times higher in Bobo-Dioulasso than in Ouagadougou with a cumulative incidence of 1:49 versus 1:59, OR = 1.51; 95% CI [1.09 - 2.10]: p = 0.013, while hemoglobinopathies C were almost 50% lower in Bobo-Dioulasso than in Ouagadougou (1:188 versus 1:66, OR= 0.56; 95% CI [0.39 - 0.79]: p = 0.001).

The observed genotype frequencies were significantly different (χ² = 50.09, p < 0.001) from the expected ones (Table 2).

The deviation is induced by the difference of 107% in the number of homozygote cases (β^S/β^S) observed compared to the expected cases (p = 0.001). For the other classes of genotypes, the observed and expected frequencies were not significantly different (p > 0.05). The allelic frequencies of β^S and β^C were 5.1 and 9.9%, meaning that the HbC variant occurred twice as often as the HbS variant (1:5 versus 1:10 newborns) (Table 3).

As shown in Table 3, when compared our results to those found in children and adolescents a fifteen year earlier, the cumulative incidence of total SCD and

χ² = 50.09, 6df, p < 0.001.

^a: Significant difference compared to current study; N, number; 95% CI, confidence interval; SCD, sickle cell disease.

homozygous SS was significantly higher in newborns (1:53 in the current study 1:57 in 2000-2004 versus 1:73 in children and adolescents). This means a decrease in the number of cases of SCD disease as age increases. However, HbC trait, homozygous CC and βC allele were most frequent in children and teenagers compared to newborns.

The purpose of this study was to assess the incidence of SCD and other hemoglobinopathies in Burkina Faso through systematic NBS. An abnormal Hb variant was found in 27.1% with a cumulative incidence of SCD of 1:53 newborns. The β^S and β^C alleles represented, respectively, about 5% and 10% of β-globin alleles in the studied population.

This study is the first to focus on NBS in another geographic and ethnic area of Burkina Faso in addition to Ouagadougou and its surroundings. It provides data to better appreciate the extent of hemoglobinopathies in the country. Indeed, in the context of poor care services, at ages beyond infancy, individuals with homozygous deleterious mutations (HbSS) are more likely to die. Moreover, those that were heterozygous trait, HbAS, and HbC due to a selective advantage for malaria, will have better survival than homozygous AA [10] [11] [12]. Therefore, NBS allows us to measure the true genotype frequencies.

However, our study has some limitations. Although Ouagadougou and Bobo-Dioulasso where the study took place, are the cities with the greatest ethnic mix (due to rural exodus), the results cannot be extrapolated to the entire country. These two major cities of the country are likely to combine several malaria spread factors (overcrowding, poor sanitation, and waste management…) that can alienate the random transmission of β-globin gene alleles across generations, due to the malaria implications discussed above. We also failed to recruit all newborns during the study period. In addition, we had not performed parental testing or molecular analysis to confirm certain findings, including thalassemia.

This study reported an incidence hemoglobinopathies of 27.1% (cumulative incidence of 1:4), confirming their importance in Burkina Faso, as previously noted [6] [7] [9]. The HbAS, and AC traits were the most prevalent and accounted for about 7.8% and 16.7%, in agreement with previous findings in the country. These results differ from those reported in Senegal and Mali, where, although the prevalence of the sickle cell trait HbAS was in the same proportions as in the current study, those of the heterozygote HbAC were much lower with 1.9% [13] and 5.6% [14] respectively. In Central Africa (Gabon, The Democratic Republic of Congo) and in Nigeria, HbAC is much rarer (1.1%, 0%, and 1.1% respectively) compared to HbAS which was 1.5 to 2 times higher than in the current study [15] [16] [17] [18]. These results confirm that the β^C allele is more concentrated in West Africa, especially around the Voltaic plateau, covered by Burkina Faso and Ghana [9] [12].

SCD was found in 1.9% of newborns, corresponding to a cumulative incidence of 1:53 newborns with a predominance of compound heterozygous SC or Sβ-thalassemia (1:73 versus 1:189 for homozygous SS). Compared with children and adolescents aged 2-25 years [6], the incidences in newborns were one-quarter (1:53 versus 1:73), two-thirds (1:189 versus 1:487) and one-sixth (1:73 versus 1:86) higher respectively for all SCD cases, homozygous SS and compound heterozygous (Table 3). These differences were not significant for compounds heterozygous. This trend confirms previous hypotheses that, in the absence of adequate health care, more than half of SCD cases are expected to die of malaria or bacterial infectious diseases by age 5 years [3]. This was particularly true for homozygous SS (61% more in newborns). For compound heterozygotes, the difference was much modest, presumably due to the natural history of this clinical form of SCD, which is more characterized by chronic degenerative complications than by acute complications [19].

The observed frequencies of Hb genotypes compared with those expected differed statistically (χ² = 50.09; p < 0.001) indicating that the distribution of these genotypes did not follow Hardy-Weinberg equilibrium. The frequency of the β^S (5.1%) and β^C (9.9%) alleles were five and ten times the theoretical equilibrium threshold of 1%. The deviation from Hardy-Weinberg equilibrium is due to the observed homozygotes (β^S/β^S) and heterozygotes (β^S/β^C) frequencies that were, respectively, 50% and 20% higher than the expected frequencies (60 cases versus 29 and 144 versus 114). Such findings have been reported previously [12] [20].

Compared to the results of the first NBS study in Burkina Faso [9], the incidences of overall homozygous HbSS, and compound heterozygotes were slightly, but not significantly (p > 0.05) higher in the current study (Table 3). This should indicate that the pool of abnormal β^S genes is maintained stable over the 15-year interval (2000-2015) between the two studies. The incidence of the HbS and the frequency of β^S allele in the two populations in Table 3 confirmed this stability. This raises the question of the lack of a comprehensive sickle cell disease program in the country, as previously mentioned by Kafando et al. [9]. However, it is relevant to note that a period of 15 years seems very short to achieve involution in a complex health problem of genetic origin such as SCD, without radical measures such as banning marriage between people at risk or terminating pregnancies with affected fetuses. This is far from being the case in Burkina Faso, given the political, ethical, and moral controversies surrounding these issues. Currently, premarital screening is not mandatory and prenatal diagnosis of SCD is neither legal nor technically feasible. Therefore, the strategy remains to focus on public awareness and newborn screening. To date, this strategy is hampered in resource-poor countries by many of the logistical and organizational barriers already discussed [9] [21]. To overcome these barriers, it is suggested that newborn screening be linked to an existing accepted program. In Benin, a strategy targeting at-risk pregnant women during prenatal consultations to sensitize them to the need to test their children at birth has shown that about 80% of women adhere [22]. In Nigeria, authors recommended that newborns screening for SCD be linked to the vaccination program [16] [23].

SCD and other haemoglobinopathies appear to be frequent in Ouagadougou and Bobo-Dioulasso. Such results call for policy decisions in favor of newborn screening in our country. Integration of such a program with other public health interventions into a large multisectoral strategic plan will facilitate its implementation and increase its potential effectiveness. A centralized approach, based on a few reference laboratories could be adopted for biological analyses, mainly confirmatory tests. Rapid diagnostic tests could be used in the first intention.

To the Pierre-Fabre Foundation for the support in the realization of this study and to all the midwives, obstetricians and pediatricians who participated in the newborn screening for SCD.

The authors declare no conflicts of interest regarding the publication of this paper.

Sawadogo, S., Nebie, K., Kima, D., Savadogo, H.T., Sanou, J.D.D., Ouedraogo, D., Ouedraogo, P., Zamane, H., Ndiaye, A. and Kafando, E. (2022) Incidence of Sickle Cell Disease and Other Hemoglobinopathies in Burkina Faso: Results of a Five-Year Systematic Neonatal Screening (2015-2019) in Four Urban Hospitals. Open Journal of Blood Diseases, 12, 87-97. https://doi.org/10.4236/ojbd.2022.124009