Newborn screening for sickle cell disease in Lubumbashi, Democratic Republic of the Congo: An update on the prevalence of the disease

INTRODUCTION

Sickle cell disease (SCD) is an inherited hemoglobinopathy resulting from the substitution of the amino acid glutamic for valine in the sixth position of the beta-globin chain.^[1] The inheritance of the sickle cell trait follows an autosomal recessive pattern. Phenotypically, only individuals with double recessive sickle cell genes Homozygous sickle cell [Hemoglobin SS (HbSS)] manifest disease, while Heterozygotes [Hemoglobin AS (HbAS)] are called carriers.

According to Diallo, Africa is the most affected continent with 200,000 newborns with SCD per year.^[2] This represents about 66.6% of children born with hemoglobinopathies worldwide. The lack of reliable data in most countries makes it difficult to estimate the actual number of people affected worldwide. There are no national registries on the disease, even in developed countries that have had newborn screening programs in place for several years (USA, United Kingdom, France).^[3] Various estimates have been published^[3-5] reporting highly variable frequencies of S allele distribution according to region: Sub-Saharan Africa (about 20 countries with 2–38%), India (6 regions with 17–30%), Eastern Mediterranean (Saudi Arabia [1–29%], and Iraq [0–22%]). In the Democratic Republic of the Congo (DRC), the latest studies report a prevalence of up to 40% of the population for the heterozygous form among carriers of the sickle cell trait (otherwise known as healthy carriers), and up to 2.3% of the population for the homozygous form among SCD patients. The DRC records about 40,000 births of children with SCD each year.^[6] According to reports from Ghana, an estimated 15,000 children are born with SCD each year.^[7] In Benin, the prevalence of sickle cell trait is estimated at 25%^[8] while in Nigeria, it varies from 24% to 25%.^[9,10] In all these African countries, the concentration of the sickle cell trait has been found to be highest in specified subpopulations,^[2,9,10] probably due to conservative tribal marriages. The autosomal recessive inheritance pattern assumed by the sickle cell trait, however, predicts changes in population-level dynamics, ease of movement, and intermarriage that would alter the distribution of the sickle cell trait within these communities.^[11]

Available data on the prevalence of SCD in a population of newborns in Lubumbashi are based on a preliminary survey conducted by Shongo and Mukuku in 2017.^[12] According to this study, the prevalence of sickle cell trait among these newborns was 15.61% (3.47% of newborns were carriers of homozygous sickle cell [HbSS] and 12.14% were heterozygous sickle cell [HbAS]).^[12]

In light of advances in health interventions, screening, and premarital counseling of the population, it is assumed that the distribution of the sickle cell trait among African populations can be strategically altered. We hypothesized that a current survey on the prevalence of SCD in Lubumbashi will be informative given that 5 years have already elapsed since the last study which was only preliminary.^[12] This study was therefore conducted to establish an update on the prevalence of the sickle cell trait in the city of Lubumbashi, in the DRC.

MATERIAL AND METHODS

RESULTS

Neonatal screening for SCD was conducted for 7 months (June–December 2020). As this was a study phase and neonatal screening for SCD is not a health policy in the DRC, the collection of blood samples was carried out according to the availability of resources and for a few hours each day. Six hundred participants were selected and 62 mothers refused to give consent for newborn screening.

Five hundred and eighty-eight blood samples were taken and analyzed from 538 newborns, of which 286 (53.16%) were boys and 271 (46.84%) were girls. All children were black Congolese. The mean chronological age at screening was 0.62 days (0–6 days). None of the newborns were transfused before screening.

The phenotypes were as follows: 369 (68.59%; 95% CI: 64.48%–72.49%) newborns were AA; 141 (26.21%; 95% CI: 22.54%–30.14%) newborns were AS; 27 (5.01%; 95% CI: 3.33%–7.22%) newborns were SS, and 1 (0.19%; 95% CI: 0.00%–1.03%) newborn was AC [Table 1].

DISCUSSION

These results, although limited to the city, have some informational value on the prevalence of genetic hemoglobinopathies in Lubumbashi. We conducted neonatal screening for SCD in five referral maternity units in Lubumbashi city. During the study period, of the 600 mothers who were sensitized in the maternity units selected for sickle cell screening of their newborns, 588 (98%) of them accepted. We believe that this acceptance rate is quite significant and would justify the implementation of systematic neonatal screening for SCD throughout the country.

The present study found that 5.01% of newborns were HbSS (homozygous SCD), 26.21% were HbAS, and 0.19% were HbAC. These results are striking given the high prevalence of SCD (5.01% HbSS) found in the neonatal population in Lubumbashi. This study follows a recent preliminary study by Shongo MY and Mukuku O^[8] in which a neonatal screening for SCD in 173 newborns screened in the maternity wards of three health facilities in Lubumbashi reported 12.14% HbAS and 3.47% HbSS. As in the present study, these authors did not find any cases of composite SC heterozygosity in their series, presumably due to the relatively low prevalence of Hb C in the general Congolese population.^[6] In the DRC, two other similar studies had already been conducted. The first, carried out on 520 newborns in 5 health facilities in Kisangani city, found that 23.3% of newborns were carriers of the sickle cell trait and 0.96% of homozygous sickle cell.^[14] The second carried out in a series of 31,204 newborns recruited throughout the country, reported that 16.9% of newborns were carriers of the sickle cell trait and 1.4% of homozygous sickle cell.^[6] The latter noted that there was no statistically significant difference between the different ethno-linguistic groups in the country, but that a high prevalence of the beta S gene was noted in tribes where the prevalence of malaria is high.^[6]

A previous study, conducted in the Great Lakes region (Burundi, Rwanda, and Eastern DRC) in four maternity wards in a series of 1825 newborns, found 0.11% of HbSS and 3.28% of sickle cell trait. The presence of Hb C was noted in 4 newborns (0.22%).^[15] In Gabon, 143 children were heterozygous (15.10%) and 17 HbSS (1.80%) in a series of 947 newborns recruited in two maternity hospitals in Libreville.^[16] In Nigeria in Benin City, Odunvbun et al.,^[17] in a series of 628 recruited neonates, found that 133 (20.6%) were AS, 7 (1.1%) were AC, 18 (2.8%) were SS, and 1 (0.2%) was SC. In view of these results, it is preferable to introduce a systematic screening of all newborns instead of targeted screening (limited to screening newborns of mothers who know their Hb phenotypes). Odunvbun et al.^[17] pointed out that mothers’ lack of knowledge of their phenotype may have led to the high level of marriage among sickle cell trait carriers, resulting in the high prevalence of SCD in their community. The impact of information and awareness on SCD, in the general population and particularly among young adolescents and adults, is very significant. This is illustrated by the example of a long-running information and education campaign in Bahrain in the Middle East, which reduced the rate of carriers of SCD by 60% in 18 years.^[18]

SCD remains unknown and ignored by the Congolese population in general and is most often equated with witchcraft; this turns patients away from the hospital, often sending them to charlatans. The disease is ignored by many, leading to stigmatization of the patients, rejection, and mockery by their peers, and by their entourage in general. Patients and their families are left to their own devices, living in unbearable and unacceptable conditions of physical and psychological suffering. The financial burden of SCD puts a strain on families who are often broken. The various methods of screening for SCD are almost non-existent in the hospitals in Lubumbashi; only a few health centers or private laboratories offer it.

CONCLUSION

SCD is very common among newborns in Lubumbashi. The present study determined the prevalence of SCD during newborn screening in Lubumbashi. The conduct of premarital counseling is essential to reduce the prevalence of this hemoglobinopathy which is very high (5.01% Hb SS). Systematic newborn screening in all maternity wards in the country would help to assess the prevalence at the national level and improve the quality of life of SCD children.