Estimating The Prevalence Of Sickle Cell Disease In Africa: A Systematic Review  

Abstract Category: Science
Course / Degree: Public health
Institution / University: University of Edinburgh, United Kingdom
Published in: 2013

Report Abstract / Summary:

Currently, genetic disorders of the haemoglobin are the most common cause of neonatal defects (Streetly et al. 2008). Sickle-cell disease (SCD) constitutes 85% of the 300-500,000 births across the globe, creating a significant worldwide health problem (Ramakrishnan et al. 2010). This is especially so in Africa where over 230 000 infants, representing 60% of overall global births are born with this defect. Accounting for 90% of disease burden, 9% of under-five mortality and an estimated annual loss of disability-adjusted life years in millions (Wonkam et al. 2012). The genetic connation of SCD has created the illusion of a low prevalence among its populace and unaffordability of evidenced-based interventions (Dyson 2011). In Kenya for example, contrary to popular opinion, Weatherfall, (2010) reported that early mortality is attributed to deaths and infection in SCD rather than malaria, demonstrating the need for action to alleviate the impending fiscal health burden. Although, less common in Southern or Northern Africa in comparison to the Western, Eastern or Central regions (Diallo and Tchernia 2002), the World Health Organisation noted the burgeoning impact of this disease in poor-resource settings (Makani et al. 2007).

This has been linked to epidemiological transitions and interventions of immunization or nutrition on childhood mortality that has improved survival rates from 98% deaths rates before medical innovation (Makani et al. 2007). These authors using anecdotal evidence reported a high prevalence of SCD among African adults (about 25% for HbS), which may suggest lower childhood mortality. Conversely, Aygan and Odame (2012) reported a 50% mortality rate among children and evidence of low survival rates in older adults. The controversial state of information highlights the lack of baseline data on the epidemiology of this disease (Makani et al. 2007). Existing information from malaria programs were generated using studies conducted in the 1970s and are similarly scarce in the developed world. This has hindered development on its diagnosis and management (Weatherfall, 2010).

Clearly, genetic blood diseases are an important public problem that have been neglected by the health sector in Africa; possibly due to other priorities and has resulted in scant information on its prevalence, mortality or clinical course (Weatherfall, 2010). However, considering the impending burden with projected population growth and demographic transition in Africa, evaluating the prevalence of this disease is pertinent to appropriate resource-allocation in effective health service planning. This will enable the implementation of evidenced-based as well as cost-effective interventions such as neonatal screening, antibiotic prophylaxis and health education (ibid).

The condition
Sickle-cell disease (SCD) denotes the chronic autosomal variant expression of syndromes due to abnormal blood genotypes; where one copy of the haemoglobin S chromosome pairs with a β-chain haemoglobin or β-thalassaemia gene (Ramakrishnan et al. 2010). This includes combinations of the sickled haemoglobin – SS, SC, Sβ+, thalassaemia, or Sβ0 thalassaemia genotypes (ibid). The polymerisation of the mutated haemoglobin as a result of de-oxygenation when passing through the blood vasculature leads to fatal complications of - vaso-occlusive crisis, haemolysis, stroke, acute chest syndrome, priapism and osteonecrosis (Aneni et al. 2013). These complications result in frequent hospitalisations, which negatively impacts on the psychological health of SCD patients (Midence et al. 1993).

Sickle-cell anaemia, the homozygous combination of beta-globin gene mutation (βs) allele, accounts for 70% of manifested cases in Africa (Aneni et al. 2013) and about two-thirds of deaths in children ≤ 5 years (Grosse et al. 2011). However, these authors noted that the methodology for deriving this estimate used the entire population figures as the numerator, rather than live births (ibid). The severity of SCD has been strongly linked with African ancestry (Ebrahim et al. 2010), alongside other contentious factors of the environment, infection and/or endemic malaria (Rees et al. 2010). Although, individuals with homozygous HbS seem to be bestowed with protection against malaria, severe forms have been documented at the same frequency among these patients as their heterozygous (Hb AS) or disease free (Hb AA) counterparts (Diallo and Tchernia 2002). This further increases their risk of crisis, consequently, driving childhood morbidity and about 50-90% of mortality (Weatherall 2010). Therefore, optimal data is vital to the institution of early screening, diagnosis and implementation of available evidenced-based strategies that have been suggested as effective means of curtailing its debilitating effect (Grosse et al. 2011).

The aim of this review is to summarise the evidence on the current prevalence of sickle-cell disease using data from Africa. It also intends to generate reliable data for foreseeable future epidemiological research; useful in burden of the disease advocacy, policymaking, improvement of awareness and management strategies (Ebrahim et al. 2010).

A literature review will be conducted to ensure the availability of sufficient research articles to perform the review. A systematic search of the literature will be performed using appropriate keywords (see table 1) identified during the scoping process. The search process will be conducted using the search terms for SCD in relevant databases (African index medicus; the Cochrane library; PubMed, Medline, Embase, global health database, web of science) from the date of inception of the database or first mention of the disease in medical literature, 1910 (Diallo and Tchernia 2002) till date (see table 2). Google scholar will be searched to ensure that relevant articles are not missed. The reference lists of key articles will be screened and if feasible, unpublished data will be requested from key researchers within this region; although this is highly unlikely (Cherry et al. 2012).

This process will be performed by two trained data abstractors to minimise the risk of errors, with a third researcher to resolve conflicting situations or discrepancies via discussions and agreement (Ibid). All the articles retrieved which meet the eligibility criteria for this review will be included. Firstly, the title and abstracts of studies will be screened and multiple publications will be reported as a single study. Then full texts of all potentially eligible papers will be retrieved for the review using the study criteria. Thereafter, data will be independently extracted from studies fulfilling the quality assessment benchmark for this study (see figure 1).

Inclusion criteria
• Population-based studies on the prevalence of SCD using cross sectional or cohort methods within an African continent will be used. No language restriction will be placed.
• Upper age limits for children over the age of 18 years will be set for this review. This is because there is a higher incidence and mortality among the younger age group as well as low prevalence in older age groups, with life expectancy of ≤ 20 years within this region (Makani et al. 2007).
• The complete numerical estimates used to calculate the prevalence rates must be available, corresponding authors will be contacted for missing data (Feigin et al. 2003)
• Published from 1900 till date
• A clear case-definition of SCD that for this purpose of this paper includes: combinations of all sickled haemoglobin genotypes (Ramakrishnan et al. 2010). While individuals without the disease include- haemoglobin AS (sickle-cell trait), haemoglobin AC or haemoglobin AA genotypes (ibid).
• A validated means of ascertaining blood group type must be clearly outlined in the studies
Exclusion criteria
• Intervention or observational studies such as case controls using adult population and evaluating other variables will be excluded.
• Hospital based or registry-based studies
• Community-based studies with non-numerical estimates,
• Studies published before 1900 review articles
• Studies using other blood genetic diseases other than SCD.
• Studies without appropriate sampling techniques
• Incomplete studies or those without a clear case definition and method of ascertaining SCD status (see table 3).

Data extraction and management
A tabulated template (see table 4/6) will be used in the presentation of results to enable succinct and systematic comparisons across the individual studies. Data on the occurrence of sickle-cell disease will be standardised to country and African population levels. Also, haematological indices on the type of SCD, study design, setting/location, demographics (age, sex) will be extracted and stored in a password-protected computer.

Quality assessment
Individual articles will be assessed by 2 independent researchers using an adapted prototype from the Newcastle-Ottawa Scale for cross-sectional and cohort studies to ensure a stringent internal and external validity of the review (see table 5) (Howard and Davies, 2007). Quality appraisal was defined on the basis of 10 criteria: relevance of the article’s study questions to the aim of this review; rigorous and clearly described methods, selecting representative samples to achieve sufficiently high response rate (set a minimum of 70%) (ibid); use of a standard approach for ascertainment of sickle-cell disease and inclusion of patients with a wide range of disease severity; exploration of the statistical significance of study results, considering all appropriate outcome measures and potential confounding factors; and overall impression of the study quality (Ramakrishnan et al. 2010).

The rating for the value of evidence supplied by the research paper was graded using a similar scale for randomised trials. Points will be assigned to each question to sum up to a total of ten points per paper. Articles scoring 10 points will be categorised as A grade, those scoring five to seven points will be categorized as B quality, and those scoring less than five points graded as C (see appendix 1 below) (Ramakrishnan et al. 2010).

Data synthesis
A narrative analysis will be used to describe trends if heterogeneity or limited data hinders meta-analysis while taking account for missing data (Streetly et al. 2008). Summary statistics of mean and percentages will be used to provide information on the frequency distribution of SCD within this region. In addition, chi-square test will be used to ascertain the prevalence odds ratio. The proportion of age-standardised differences for children below the age of 5 and above will be estimated using 95% CI to aid comparison in the different mortality rates within these age-bands (ibid).

Interpretation of data
The comprehensive search process using a systematic approach during the study selection, quality appraisal and data extraction will ensure the generation of robust estimates on the epidemiology of this disease (Anandan et al. 2010). Although, the inclusion of the African index medicus will improve the validity of the study, electronic searches may not identify all relevant articles. Moreover, many of the articles from endemic regions may not be indexed in major journals, resulting in publication bias. This could reduce the effect measure, by yielding lower prevalence ratios. In addition, the modification of a previously validated tool may affect the study quality and certain limitations inherent in the individual studies may influence the strength of the data produced. Heterogeneity in data alongside the added difficulty or unavailability of high-quality research in this region may pose major limitations of generating estimates. This may be result in an unrepresentative sample of at risk groups and limited evidence may hinder the ability to suggest robust recommendations (ibid).

Nevertheless, the information, though limited would serve as a provisional guide in stimulating concerted government efforts on reducing the impact of SCD (Weatherall, 2010). It would raise awareness or stimulate political will to act and inform policy that would lead to the execution of available preventive services of neonatal screening, premarital counselling and advocacy (Aygan and Odame 2012). Furthermore, it would serve as baseline data for the evaluation of the effectiveness of potential interventions. This could aid in fostering international collaboration on research to develop context-specific programs requiring funding and capacity building (Weatherall 2010).

Critical reflection
Reflective thought processes were perhaps employed during and after the completion of this protocol. It helped to make sense of the procedure and showed gaps in what I intended doing and could actually achieve. The overall course of designing this protocol was quite a task, sometimes perturbing, but also enlightening. On the other hand, because this protocol was hypothetical with no personal experience from real world research to inform my decisions, this may have influenced the way this protocol was designed.

For example, fiscal resource, time and expertise may hinder the use of articles published in other languages used for African research. Hence, in reality I may have restricted my inclusion criteria to English studies alone. Nonetheless, it highlighted the essential role of in-depth thinking and research to develop a relevant public health question within existing literature without replicating knowledge. My decision on the topic was influenced by gaps in the literature and its relevance to the chosen region. This underscored my understanding that the research question and objective of the systematic review directs the core of the project.

I also performed a small scale literature search to ensure that the project was feasible; with no existing protocol or review on this topic area. None exists, although this may be a reflection of my developing searching skills. Also, due to the paucity of research and the cost of conducting cohort studies, routine data should have been included and separately analysed (Grosse et al. 2011). However, the unequal access to healthcare and the widespread use of private health services would largely affect the disease burden estimates derived; the use of unpublished data was included instead. Furthermore, a huge amount of detail was required to ensure the use of standardised methods in the review process to make sure the study was replicable and robust. This was difficult to determine due to the limited time frame and human resource. For example, finding an appropriate appraisal tool for observational studies was quite a task in comparison to the large number of tools for experimental studies. However, this was resolved by reference to previous research, to ensure that the appropriate tools and procedures were employed. This illustrated that closing research gaps, is not an independent exercise, it remains within the context of previous work.

Hence, an existing tool was adapted and used instead, adding components such as ethical approval due to its key relevance in present day bio-medical research. Moreover, achieving the goal of summarising evidence, translated into statements that would inform the direction of research, policy or practise is also an ethical responsibility. The pre-defined criteria set by the protocol will potentially reduce bias of selecting favourable papers. Although, changes are unavoidable, and this can introduce bias of its own kind, transparency in the documentation process would allow for correct interpretation of results. I realised the need for accountability during the design process of the protocol as every study design has an inherent risk of bias. However, this decision-making process would most likely be flawed if the appraisal of articles is conducted by a single researcher.

Furthermore, though data synthesis using narrative analysis may cope with heterogeneous data it may be unreliable due to the absence of a definite standard for analysis and may be affected by my skills during the process - hence the need for rigour, feasible with collaboration from experts in the specific field and methodology. I came to appreciate the amount of effort involved in conducting systematic reviews. Overall, this has improved my critical appraisal skills and possibly, my ability to engage in the process of conducting a review. These skills would be invaluable in my career in informing evidenced-based practice and in the process of continual professional development.

Report Keywords/Search Tags:
sickle cell disease, review, prevalence, community-based study, population-based study,

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Submission Details: Report Abstract submitted by Jacqueline Thompson from United Kingdom on 20-Jun-2013 00:00.
Abstract has been viewed 3217 times (since 7 Mar 2010).

Jacqueline Thompson Contact Details: Email: jacqwued7@gmail.com

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