Impact of Sickle Cell Disease on Affected Individuals in Nigeria: A Critical Review

Abstract

Sickle cell disease is an autosomal recessive disorder of the beta-globin gene, with resultant deformation of the red blood cells and variable clinical outcomes. Nigeria is recognised as the country with the highest burden of sickle cell disease globally. This study aimed at critically reviewing available literature on impact of sickle cell disease in Nigeria. A literature search was carried out on four databases, and a total of 116 articles that met the inclusion criteria were included in the critical review.

It was observed that majority of the studies were carried out in South-Western part of Nigeria (47.4%), whilst the North-East had the least number of studies undertaken in this area, more than a quarter of the studies (27.6%) were related to hematologic and serologic screening. Major themes that emerged from this review were morbidity and mortality; prevalence of sickle cell disease; issues relating to blood transfusion; psychosocial impact; and anatomical dysfunction in sickle cell disease.

Intervention programs from both government and non-governmental organizations aimed at reducing the burden of sickle cell disease and its socio-economic impact were identified as key to strategies aimed at overcoming challenges associated with the disease. Findings from this study also revealed that education and awareness interventions were central to reducing the prevalence of sickle cell disease in this setting.

Keywords:

sickle cell anemia, public health, hematology, genotype, hemoglobin, gene, red blood cell, Vaso-occlusive crises

Introduction

Sickle cell disease is an autosomal recessive disorder of the beta-globin gene, with resultant deformation of the red blood cells and variable clinical outcomes. Nigeria is recognised as the country with the highest burden of sickle cell disease globally.

Sickle cell disorder is by far the commonest inherited disorder in the world and three quarters of cases occur in Africa. In Nigeria, where it affects two out of every hundred children born, it causes suffering for innumerable patients and their families. However, despite its importance, until now there has been no dedicated sickle cell center in Africa. This is partly because the very scale of the problem makes it difficult to see how to start.

Sickle cell disorder is an inherited haemoglobin disorder comprising sickle cell anaemia (Hb SS) and some less prevalent but related conditions such as sickle haemoglobin C disorder (Hb SC) and sickle beta thalassaemia (Hb SBthal). The genes for these conditions arose by mutation but proliferated in areas where there is or there was a high incidence of falciparum malaria, the most lethal strain of malaria known to man.

The basic pathophysiology of sickle cell disease involves the de-oxygenation and polymerization of red blood cells, leading to deformation and hemolysis. This therefore gives rise to varieties of clinical manifestations such as acute pain episodes and anemia. The hallmark of sickle cell disease is Vaso-occlusive crises, and it is the most common reason for frequent hospital visits for persons affected with the disease.

Sickle cell disease has been recognized by the United Nations General Assembly as a disease of global public health concern. It is noteworthy that 20 to 25 million people are affected with sickle cell disease globally, out of which between 12 to 15 million reside in Africa, whilst developed countries only account for 10% cases.10 Sub-Saharan Africa accounts for the highest percentages of various indices associated with sickle cell disorder. It accommodates 75% of all patients with sickle cell disease and 70% of all sickle cell disease births globally, with some of the affected children dying before the age of 5 years.

Nigeria is believed to be the most sickle cell endemic country in sub-Saharan Africa with between 2% and 3% of the total population affected. This study aimed at critically reviewing the impact of sickle cell disease in Nigeria, alongside relevant emergent issues. The critical review strategy can help assess the impact of sickle cell disease holistically and provide policy direction for government in improving the quality of care for individuals with the condition.

Methods

Data Sources and Search Strategy

A detailed literature search was undertaken to identify publications that focused on sickle cell disease in Nigeria. Relevant articles were searched, screened, and included in this study accordingly. Articles were searched through Web of Science, PubMed, Google Scholar, and African Journal Online using different combinations of keywords which includes “sickle cell disease”, “sickle cell anemia”, “Nigeria” “burden” and “impact”. All the four databases were carefully searched for only English-language full-text original articles published. Titles and abstracts of the retrieved documents were examined to identify those that were within the area of focus.

Review Selection

After the exclusion of duplicate literature, titles and abstracts of selected articles were carefully reviewed. All relevant full-text studies obtained were assessed for eligibility. Original articles from peer-reviewed scientific journals with primary data on various areas that focused on the impact of sickle cell disease in Nigeria were considered potentially eligible for inclusion in this review. All studies outside Nigeria were excluded.

Data Extraction and Analysis

Data were extracted from the selected studies into an Excel spreadsheet (Microsoft Office Excel 2013). The variables registered for each article were author, year of publication, name of the journal, and article title. Others include area of focus, geopolitical zone, method of data collection and age range of subjects. Data were then imported into Statistical Package for Social Sciences software version 25 for descriptive analysis, and results were summarized as figures.

Variables

five major variables were used in study outcome prediction. They include: the causative agent variables which in this study is the hemoglobin variants (i.e., SS and SC); the host variables or biodata (i.e., age, gender); environmental variables (i.e., referral clinical departments such as A/E, CHER, CHOP, GOPD, HAEM, ANC, PHD and SOPD); seasonal (time) variables

(January-December) and causative agent-related variables such as anemia grades based on levels of hemoglobin (Hb) concentration such as mild (Hb = 10.0-12.9 g/dL), moderate (Hb = 7.0-9.9 g/dL) and severe (Hb≤7.0 g/dL); ABO-Rhesus blood groups (Groups A, B, AB, O, Rh positive or Rh negative) sickle cell trait (AS) and non-SCD hemoglobin variant (i.e., AA). The dependent variables in this study were referral clinical departments, time of diagnosis of SCD during the study years, while independent variables were age and gender.

Bibliometrics

Sickle Cell Disease Studies by Geopolitical Zone shows the various geopolitical zones with their respective percentage of studies on sickle cell disease in Nigeria. It was observed that a considerable proportion of the studies (55; 47.4%) were carried out in the South-West zone. A total of ten studies were carried out each in North-Central, North-West, and South-South, whilst 20 studies were recorded in South-East.

Data Driven Thematic Explorations of Sickle Cell Disease

Heart rate variability and electrocardiogram reports had also been investigated among sickle cell disease patients. Adebiyi et al reported a reduction in heart rate variability among patients with vaso-occlusive crises. Significant electrocardiographic abnormalities were also reported among patients with sickle cell disease.

Morbidity and Mortality in Sickle Cell Disease Findings by Akingbola et al revealed varying degree of abdominal pain among sickle cell disease patients with multifactorial etiology. Some identified factors responsible for abdominal pain include retroperitoneal lymph node enlargement, bone marrow hyperplasia, hepatobiliary disease, splenic disorders, and mesenteric arterial thrombosis.
Mortality in sickle cell anemia patients was linked to bacterial infection, necessitating the need for proper treatment with appropriate antibiotics. Some bacteria commonly associated with mortality in sickle cell anemia include Streptococcus pneumonia, Salmonella species, and Hemophilus influenza.

Discussion

Findings from this review revealed that data utilized for majority of the studies were collected via laboratory tests. Only one out of the reviewed studies adopted a qualitative approach through the use of interviews. This suggests that knowledge gaps may exist, especially in areas where interpretivist epistemologies are best suited to improve practice. Qualitative data collection can encourage communication on critical issues which may be difficult to express in quantitative form. Interpersonal interview has been found to increase confidence as well as clinical outcomes for patients. It is, therefore, critical for more qualitative research be considered in undertaking studies that aim at better understanding sickle cell disease, with a view to improving its management.

A considerable proportion of the studies focused on hematological and serological screening, and this could be due to the fact that sickle cell disease is primarily a blood disorder.Similarly, significant problems associated with white blood cells, platelets, and coagulation in sickle cell anemia condition could be responsible for the extensive research in this area. Another factor that could have contributed to the preponderance of research in this area could be the routine serologic evaluations of sickle cell patients’ body electrolytes, liver enzymes, as well as micro and macro nutrients.

Sickle cell disease poses a serious burden to Nigeria’s health system and the society at large. In this study, various pathophysiologic effects associated with this condition were identified. Findings revealed relatively lower arterial blood pressure in patients with sickle cell anemia.Furthermore, indicators such as hematocrit, frequency of crisis, body mass index, and body surface area emerged as significant determinants of blood pressure issues for people affected with the disease Additionally, peripheral vascular resistance was identified as a determinant of blood pressure in patients with severe anemia.

Findings from this study suggest the presence of electrocardiographic abnormalities among patients with sickle cell disease. Electrocardiographic abnormalities observed among these individuals were attributed largely to chronic anemia and vaso-occlusion. Chronic anemia was believed to be responsible for increased cardiac output with a minimal increase in heart rate. Progressive vasculopathy occurring as a result of inflammatory cytokines and oxidative stress was reported to be associated with sickling and intravascular hemolysis, and this also contributed to progressive cardiac lesions with subsequent abnormal electrocardiographic readings.

Study site

this study was carried out at the Federal Medical Center, Umuahia (FMCU), Abia State, south-eastern Nigeria. It is a 350-bed tertiary health center. It is a center of excellence in the research and management of sickle cell disease in the region. The hospital serves as a referral center for inhabitant of Abia State and their neighboring states of Imo, Anambra, Enugu, Ebonyi, Cross Rivers, Akwa-Ibom, and Rivers States. These states account for about 20% of the Nigerian population based on 1991 population census.

Limitation and Strength

The possible limitation of this review is associated with the search strategy that was limited to the title, keywords and abstract of each article. More in-depth search could have perhaps resulted in identification of more studies. Despite this potential weakness, the review adopted a robust method of analysis through the use of a combination of both descriptive statistical analysis and narrative analysis in the synthesis of various outcomes, and presentation of relevant findings. Further research to determine relevant interventions to cushion the relevant impacts identified in this review can be invaluable in reducing the burden of sickle cell disease in Nigeria.

Conclusion

This study adopted a novel approach to critically review issues relating to sickle cell disease and its health impact on affected individuals in Nigeria. Majority of the articles in this review were undertaken in the South-Western part of the Country, and a considerable proportion of them involved laboratory investigations. Findings from the study revealed that sickle cell disease had both health and social consequences.

The disease was identified as a major healthcare issue in Nigeria, given that the country had highest prevalence of sickle cell disease globally, while also contributing to significantly high mortality rates of children under 5 years of age. Key aspects of disease reduction and elimination strategies for sickle cell disorder in Nigeria include continuous enlightenment programmes; social awareness campaigns; and premarital genetic counselling about the condition.

It is also critical to establish more sickle cell clinics with adequate state of the art equipment and well-trained personnel for prompt diagnosis and treatment of various clinical manifestations of sickle cell disease. Further health system-wide measures that can help control and eliminate the disease include free routine genetic screening as well as psychosocial and financial support for persons with sickle cell disease.

It is important for sickle cell patients to have access to critical services like stroke risk screening with transcranial doppler ultrasound and pulmonary hypertension risk with echocardiography. Also, it is important to prioritise access to relevant affordable therapies such as hydroxyurea, niprisan, prophylactic antibiotics, antimalarials and other medications.

A synergistic implementation of these interventions identified in the study will not only help reduce sickle cell morbidity and mortality for Nigerians with sickle cell disease, they would also make a significant contribution towards controlling and elimination of the disease. The innovative study design adopted by the study enabled the identification of thematic areas, geopolitical zones, methodological approaches and disease specifics neglected by the extant literature. Further robust research in these critical areas can yield strong contextual evidence that will underpin comprehensive strategies for sustainable and impactful policy and practice reforms.

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