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Abstract
Objective This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and educational outcomes of children and adolescents in sub-Saharan Africa.
Design A systematic review and meta-analysis was used.
Data sources Five databases, namely, MEDLINE, Scopus, Web of Science, Cochrane Library and Google Scholar, were systematically searched for relevant articles up to 23 August 2023.
Eligibility criteria It was focused on randomised controlled trials involving children and adolescents in sub-Saharan Africa, exploring the effects of iron supplementation on various outcomes, such as serum ferritin and haemoglobin levels, anaemia, mental health and school performance.
Data extraction and synthesis The Joanna Briggs Institute Critical Appraisal tools were used for quality assessment, with two independent reviewers thoroughly evaluating each paper. Using the Cochrane risk of bias tool, we evaluated the certainty of evidence such as the risk of bias, inconsistency, indirectness, imprecision and publication bias.
Results A systematic review of 10 articles revealed that WIFAS significantly increased serum ferritin levels in adolescent girls (Hedge’s g=0.53, 95% CI 0.28 to 0.78; heterogeneity I2=41.21%, p<0.001) and haemoglobin levels in school-aged children (Hedge’s g=0.37, 95% CI 0.01 to 0.73; heterogeneity I2=91.62%, p<0.001). The analysis further demonstrated a substantial reduction in the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; heterogeneity I2=28.12%, p<0.001).
Conclusion WIFAS proved effective in enhancing serum ferritin and haemoglobin concentrations and lowering the risk of anaemia in school-aged children and adolescents compared with a placebo. Similarly, there are not enough studies to examine the effects of WIFAS on school performance. However, information regarding mental health problems, mortality and potential side effects remains insufficient.
PROSPERO registration number CRD42023397898.
- Adolescent
- Anaemia
- Public health
- MENTAL HEALTH
- NUTRITION & DIETETICS
- PAEDIATRICS
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Hedge’s g addresses the issue of overestimation of the effect size in small samples.
Certainty of evidence for serum ferritin, haemoglobin and anaemia is moderate.
Incorporation of five databases to search for articles.
Diverse intervention designs, spanning dose and iron supplement form contributes to complexity.
Substantial differences in intervention design, including dose, form of iron supplements, and frequency and duration of supplementation, add complexity.
Introduction
Adolescents are a subset of children whose age ranges from 10 to 19 years.1 This age group makes up the greatest proportion of the population (23%) in sub-Saharan Africa, which is about twice that of the industrialised countries.2 Adolescence, marked by the transition to adulthood, is a critical phase characterised by significant growth, behavioural maturation and sexual development. This represents the second growth spurt in life, particularly for girls who undergo unique experiences including menstruation, emotional changes, nutritional requirements and identity formation. Adolescents require heightened nutritional demands, with a specific emphasis on the need for iron. This period lays the foundation for adult health and economic well-being. Adolescents attain 20% final adult height and 50% adult weight, underscoring its pivotal role in shaping future health outcomes.3 4
Anaemia, a widespread global health concern, impacts approximately 1.6 billion individuals. According to the WHO, approximately 50% of anaemia cases are attributed to iron deficiency.5 Moreover, the prevalence of anaemia in sub-Saharan Africa surpasses 39%.6 This condition serves as a direct marker of undernutrition and insufficient iron intake, posing a significant public health challenge for adolescents.7 Iron plays a crucial role as an essential nutrient in the development and functioning of the brain. Its functions are diverse and contribute to various aspects of neural activity and neurotransmission. Some key roles of iron in the brain include ATP production, synthesis and packaging of neurotransmitters, and uptake and degradation of neurotransmitters.5 8
Iron-deficiency anaemia (IDA) in adolescence has the potential to impede growth, hinder motor and brain development, and increase the risk of illness and mortality. Failure to promptly address anaemia during this critical period may lead to persistent challenges later in life9 including limiting their educational achievements and subsequently impacting their economic potential.4 10 11
Adolescents are particularly prone to IDA due to a range of factors, including rapid growth, insufficient dietary iron intake, reduced bioavailability of dietary iron and heightened susceptibility to infectious diseases, parasitic infections and menstrual blood loss.7 The combination of these factors contributes to an increased risk of IDA in adolescent girls, emphasising the need for targeted interventions and education to address the specific challenges faced by this demographic group.10
Indeed, adolescence and school-aged children are recognised as a pivotal period for implementing interventions to address anaemia and lay the foundation for future health, particularly in terms of childbearing.1 2 Implementing iron supplementation as an effective strategy to combat iron deficiency can have a substantial impact on reducing the prevalence of anaemia, improving public health outcomes and enhancing the well-being of affected populations, particularly in resource-constrained settings.12–14
Following the robust literature review, there is a notable scarcity of information regarding the effectiveness of once-weekly IFAS concerning a broader spectrum of school performance and health outcomes including mental health.9 The limitations of the available data underscore the need for comprehensive and standardised research methodologies to elucidate the full range of effects associated with weekly iron-folic acid supplementation (WIFAS) on diverse nutrition, education and health parameters. Within the framework of this systematic review and meta-analysis, we aimed to assess the impact of once WIFAS on serum ferritin levels, school performance, and mental health status among children and adolescents in the sub-Saharan African region.
Methods
Searching strategies
The review encompassed a comprehensive examination of various literature sources through an extensive search across four electronic databases, supplemented by a manual search of references from key articles, previous reviews and grey literature, to thoroughly investigate the effects of WIFAS on serum ferritin levels, school performance and mental health. Our search for published articles was confined to individuals aged 6–19 years and studies conducted exclusively in sub-Saharan Africa. We systematically searched international databases, including Scopus, Web of Science, PubMed (MEDLINE), Cochrane Library and Google Scholar. The search terms were combined using Boolean operators ‘AND’/‘OR’ (online supplemental material 1). All published articles up to 23 August 2023 were incorporated into the systematic review. The results of the database search were aggregated, and duplicate articles were eliminated using the online Rayyan Software (https://www.rayyan.ai/). This tool was also employed to download the full text of studies for further evaluation
Supplemental material
Eligibility criteria
Inclusion criteria
Study area
Only studies conducted in sub-Saharan Africa (South of the Sahara).
Publication condition
Articles published in peer-reviewed journals.
Study design
All randomised control trials and clinical trial studies.
Intervention
WIFAS.
Language
Articles published in the English language.
Age
School-aged children typically encompass a range of ages, including the adolescent group.
In this study, individuals aged between 4 and 19 years, and both primary and secondary school children were included.
Exclusion criteria
Studies conducted related to iron fortification, and studies lacking specific outcome reporting were excluded from our analysis.
Outcome measurement
In this study, the main focus was on evaluating the impact of WIFAS on key health indicators, including serum ferritin levels, haemoglobin (Hgb) concentrations, anaemia prevalence, mental health and school performance. Measurement of outcomes involved assessing serum ferritin (in μg/L) and Hgb (in g/dL) through mean and SD calculations. For anaemia, the prevalence was examined as binary outcomes postsupplementation. Moreover, the study delved into the assessment of school performance by considering the average scores of subjects, school grades and school attendance increment. Additionally, cognitive performance was thoroughly evaluated using a battery of cognitive tests specifically chosen, designed or adapted for the age and cultural group under consideration. This battery included four subtests from the Kaufman Assessment Battery for children aged 3–18 years, second edition (KABC-II)15 and the Hopkins Verbal Learning Test.16 The subtests chosen from the KABC-II encompassed the Atlantis (assessing working memory) and Atlantis Delayed (evaluating long-term memory and retrieval) tests from the learning scale, the Hand Movement test (measuring short-term memory) from the sequential processing scale and the Triangles test (assessing visuospatial cognition) from the simultaneous processing scale.17–19
Data extraction
The extraction of data was carried out independently by two authors (SK and BM) using a standardised spreadsheet for data extraction. The format for data extraction encompassed details such as the primary author, year of publication, the geographical region where the study was conducted, sample size, frequency of supplementation, age, sex, dose of supplements, outcome measurement, duration of the intervention and information related to the randomised controlled trials (mean, SD, median and IQR proportion).
Quality assessment
For the assessment of the methodological quality of the included studies, we employed the Joanna Briggs Institute (JBI) Critical Appraisal tools designed for use in systematic reviews of randomised controlled trials.20 This tool consists of thirteen questions addressing aspects such as selection bias, attrition bias, performance bias and detection bias. Two independent reviewers (SK and BWA) meticulously assessed each paper, engaging in discussions to resolve any discrepancies. In cases where disagreements persisted, a third reviewer (KH) was consulted to arbitrate and ensure consistency between the two independent reviewers. We have also contacted authors through email to get some outcome measurements that are mentioned by mean and median, as well as full texts. Each question in the JBI Critical Appraisal tools was assigned a score: ‘yes’ received a score of 2, ‘no’ was scored as 0, ‘unclear’ was denoted as 1 and ‘not applicable’ was recorded as NA. The overall quality of the studies was determined based on the cumulative score, classifying them as high quality if they scored 20 and above, good quality for scores between 13 and 19, and lower quality for scores below 13. The detailed results, including the breakdown of scores for each study, can be found in table 1. Notably, nearly half of the studies (47%) achieved a high-quality score while 11.7% were categorised as lower quality (online supplemental table 1).
Supplemental material
Descriptive summary of the studies included in the systematic review and meta-analysis among adolescents in sub-Saharan Africa, 2023
Statistical analysis
The extracted data were entered into the computer using an Excel sheet and imported to STATA V.17 for analysis. Heterogeneity among reported was assessed by using the Higgins-I2 with Cochran Q statistic at 25%, 50% and 70% as low, moderate and considerable heterogeneity respectively with p values less than 0.05.21 A random effects meta-analysis model was used to estimate the pooled effect of WIFAS on serum ferritin level, Hgb, anaemia, school performance and mental health. A forest plot was also used to visualise the presence of heterogeneity subjectively. Possible differences between studies were explored by subgroup analyses and sensitivity analysis. Descriptive statistics (means and SD, median, IQR, 95% CI and proportions) were used to summarise baseline information. The finding was presented using a forest plot with respective hedges and risk ratios and 95% CIs. Evidence of publication bias was assessed using both Egger’s and Begg’s tests with a p<0.05 as a cut-off point to declare the presence of publication bias.22 23 The pooled hedges and risk ratios with 95% CI for each factor were used.
Registration and reporting
This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023397898). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during the systematic review process.24
Result
We identified a total of 2026 articles of which 1945 were from Scopus, Web of Science, PubMed, Cochrane Library and 81 from Google Scholar. After excluding 343 duplicates, a review of titles and abstracts against the review objectives and inclusion criteria led to the exclusion of 1631 articles as irrelevant. Subsequently, the full texts of the remaining 52 studies were assessed, with 10 studies meeting the criteria for inclusion in the present systematic review and meta-analysis (figure 1).
PRISMA flow diagram illustrating the study selection process of iron and folic acid supplementation effect on iron status, mental health and school performance articles. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Study characteristics
The current systematic review and meta-analysis was carried out in sub-Saharan Africa. Among the included studies, four were conducted in Eastern Africa,25–28 with one study in Ethiopia, one in Kenya, one in Tanzania and one in Mozambique. Additionally, three studies were conducted in Western Africa,29–31 with one in Mali, one in Burkina Faso and one in Ghana. Moreover, two studies were carried out in Southern Africa,32 33 with one in Zambia and one in South Africa. Furthermore, a study was conducted in North-East Africa Sudan.34
Besides, concerning the frequency of supplementation, all of the studies were included on a weekly basis,25–34 and seven studies were included that primarily focused on adolescent girls.25–29 31 34
Regarding the supplement composition, four studies were conducted on 60 mg of elemental iron and folic acid in amounts ranging from 0.4 mg to 2.8 mg.26 28 29 31 Two studies were conducted in the form of 65 mg elemental iron and folic acid amounts ranging from 0.1 mg to 0.25 mg.30 32 Moreover, two studies were conducted in the form of ferrous sulfate,27 33 one study in the form of 120 mg elemental iron25 and one study did not know the dosage.34 Only three studies were conducted in community based.27 30 35The supplementation period varied within the range of 2.2 months to 18 months (table 1).
Effect of WIFAS on serum ferritin-narrative synthesis
Four studies assessed the impact of WIFAS on serum ferritin26–29 using various statistical measures, including mean, SD, median and IQR. Out of these, three studies reported a significant improvement in the serum ferritin level of children with IFAS.25–27 However, a study conducted by Gies et al 29 did not find a significant effect between IFAS and serum ferritin. Furthermore, three studies demonstrated that once-weekly IFAS led to a significantly greater increment in serum ferritin compared with the control group, with the favour of 9.1 µg/L, 39.1 µg/L and 13.3 µg/L, respectively.25–27
Effect of WIFAS on serum ferritin-meta-analysis
Three studies were incorporated into the meta-analysis,25–27 involving a total of 440 adolescent girls. Among them, 205 received weekly iron supplementation while 235 were assigned to the placebo/non-intervention group. The analysis revealed a positive impact of weekly iron supplementation on enhancing the serum ferritin levels of adolescent girls (Hedge’s g 0.53, 95% CI 0.28 to 0.78; test for heterogeneity I2=41.21%). There is no publication bias with p value of 0.374 (figure 2).
Meta-analysis of the effect of once-weekly IFAS on serum ferritin. IFAS, iron-folic acid supplementation; REML, Random Effect restricted maximum likelhood.
Effect of WIFAS on Hgb-narrative synthesis
In this comprehensive review, 10 studies were incorporated to evaluate the impact of WIFAS on Hgb levels. Out of these, five studies administered IFA every week,25 28 30 31 35 revealing a significant increase in Hgb concentration ranging from 0.12 g/dL to 4.8 g/dL. However, three studies did not significant association between WIFAS and Hgb concentration.27 29 33
Effect of WIFAS on Hgb-meta-analysis
In this meta-analysis, a total of 5 studies25–27 30 33 involving 1949 school-aged children, including adolescents, were included. Among them, 933 received weekly iron supplementation while 1016 were part of the placebo/non-intervention group. The analysis demonstrated a significant effect of weekly iron supplementation in improving the Hgb levels of school-aged children (Hedge’s g 0.37, 95% CI 0.01 to 0.73; test for heterogeneity I2=91.62%). There is no influential study and publication bias (p value of 0.924) (figure 3).
Meta-analysis of the effect of once-weekly IFAS on haemoglobin. IFAS, iron-folic acid supplementation.
Effect of WIFAS on Hgb-subgroup meta-analysis by setting
The subgroup analysis revealed that both school25 27 30 33 and community26 setting supplementation of iron had a significant effect on the Hgb levels of school-aged children. Additionally, the variability among the studies was within an acceptable range for both the school setting supplementation (Hedge’s g 0.23, 95% CI 0.12 to 0.35; test for heterogeneity I2=16.33%) and the community setting (Hedge’s g 1.28, 95% CI 0.97 to 1.58) (online supplemental figure 1).
Supplemental material
Effect of WIFAS on anaemia-narrative synthesis
In this systematic review, an analysis of seven studies was conducted to evaluate the impact oIFAS on the prevalence of anaemia. Out of these, three studies implemented IFAS every week,28 32 36 demonstrating a significant reduction in the prevalence of anaemia, with percentages ranging from 0.35% to 8.2%. However, the findings from the remaining three studies did not show a significant association between WIFAS and the prevalence of anaemia.28 29 33 Despite our efforts to obtain the full-text article through email correspondence with the author, we were unable to secure it. Nonetheless, we relied on information from a conference proceeding abstract paper conducted in Sudan. According to this abstract, intermittent iron with folic acid supplementation demonstrated a significant (65.7%) reduction in the likelihood of anaemia in the experimental group when compared with the control group, which received folic acid alone.34
Effect of WIFAS on anaemia-meta-analysis
In this meta-analysis, 4 studies25 29 30 33 were included, comprising a total of 2505 school-aged children, including adolescent girls. Among them, 1233 received weekly iron supplementation in the treatment group, while 1272 were assigned to the placebo/non-intervention group. The analysis demonstrated a significant impact of weekly iron supplementation in reducing the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; test for heterogeneity I2=28.12%). Moreover, there is no publication bias on the effect of WIFAS on anaemia with a p value of 0.798 (figure 4).
Meta-analysis of the effect of once-weekly IFAS on anaemia. IFAS, iron-folic acid supplementation.
Effect of WIFAS on school and cognitive performance-narrative synthesis
In this systematic review and meta-analysis, we could not get enough studies regarding the effect of WIFAS on school and cognitive performance. Despite our efforts to secure the full-text article through email correspondence with the author, it remains unavailable. However, we relied on information from a conference proceeding abstract paper conducted in Sudan. According to this abstract, intermittent iron with folic acid supplementation did not show a significant association with school performance in the experimental group when compared with the control group, which received folic acid alone.34
Effect of WIFAS on mental health problem: narrative synthesis
No trials were reported in this outcome in sub-Sahara Africa.
Certainty of evidence
To evaluate the certainty of evidence, we considered factors such as risk of bias, inconsistency, indirectness, imprecision, publication bias and additional considerations like large effect, dose-response and confounders. The assessment of risk of bias used the Cochrane risk of bias tool for 2019, encompassing criteria such as sequence generation, allocation concealment, blinding/masking of the intervention, intention-to-treat analysis, blinding/masking of outcome assessors and freedom from other biases.35 Inconsistency was explored through the heterogeneity (I2 of the overall effect in the meta-analysis). Indirectness was scrutinised for external validity or generalisability (PICO, Population, Intervention, Comparition and Outcome of inters), applicability and any deviations from the research question. Imprecision was investigated through wide CIs, including those indicating a null effect and high relative risk (RR>0.75 or >1.25). Additionally, we assessed publication and other biases. Based on our findings, we moderately recommend that WIFAS increases serum ferritin and Hgb levels while reducing anaemia (online supplemental table 2).
Discussion
The current study incorporated 17 randomised trials in a systematic review to assess the impact of WIFAS on various health indicators including serum ferritin, Hgb, anaemia, mental, school and cognitive performance. The trials were distributed across East Africa (four studies), Southern Africa (two studies), West Africa (three studies) and Northern Africa (one study).
The current meta-analysis revealed the positive effects of WIFAS on serum ferritin and Hgb levels. Additionally, the WIFAS demonstrated a reduction in anaemia. These findings are consistent with findings from a study done by De-Regil et al. This suggests that intermittent iron supplementation is effective in improving Hgb concentrations and reducing the risk of anaemia or iron deficiency in children under 12 years of age.9 The findings of De-Regil et al about intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women supported our findings.9
The findings of our study align with the WHO recommendations, supporting the guideline that advocates for the intermittent use of iron and folic acid supplements as a public health measure. This recommendation aims to reduce anaemia and enhance iron status among menstruating women, emphasising the global significance of evidence-informed strategies in addressing nutritional deficiencies.36 Furthermore, our findings are consistent with the recommendation advocating for WIFS. This approach serves as a preventive and sustainable long-term strategy for improving iron status and reducing the prevalence of anaemia. The positive outcomes observed with WIFS align with the ‘mucosal block’ hypothesis. According to this hypothesis, administering iron every week allows sufficient time for the shedding of cells loaded with iron from a previous dose. This shedding process contributes to increased iron absorption, reinforcing the efficacy of the WIFS approach.37 38
UNICEF’s latest nutrition strategy, released in 2021, incorporates WIFAS as an intervention in the result area focusing on ‘middle childhood and adolescents’.39 Nutrition guidance specific to this target group has also been issued by UNICEF.40 In regions where the prevalence of anaemia among menstruating adult women and adolescent girls falls within the range of 20%–39.9%, the guidance recommends weekly supplementation of 60 mg of elemental iron and 2800 µg of folic acid for 3 months, followed by 3 months of no supplementation, and then restarting the supplementation. It further suggests that, if feasible, intermittent supplementation should continue throughout the school calendar year in these settings.
A subgroup analysis was conducted to examine the distribution modalities of iron-folic acid supplementation programmes, distinguishing between school-based and community-based approaches. The results revealed that only one study focused on community-based distribution, demonstrating a positive impact on Hgb levels. Whereas, five studies centred on school-based modalities and indicated a favourable effect on Hgb levels. These findings prompt a discussion on comparing the feasibility of implementing iron-folic acid supplementation programmes in schools versus communities, considering factors such as accessibility for adolescent groups and cost-effectiveness. More than 90% of adolescents are now found in schools and cost-effective in school settings.41 Hence, distributing WIFAS at school modalities is beneficial compared with the community.
The systematic review indicates that IFAS has a positive impact on school attendance and cognitive performance. This aligns with assessments from the WHO and Copenhagen Consensus Challenge, which estimate a high benefit-to-cost ratio for iron interventions. The ratio is based on resource savings, enhancements in cognitive development and schooling, and increased physical productivity, reaching as high as 200:1. Emphasising the prevention of IDA in adolescents is strategically crucial, considering potential gains in physical capacity, cognitive ability, and, for adolescent girls, improved pregnancy outcomes and intergenerational benefits.42 43 However, mental health trials were not reported in this outcome in sub-Sahara Africa.
Given the positive impact of WIFAS on improving iron status and reducing anaemia, policy-makers must prioritise the implementation of such programmes in public health initiatives. Ensuring access to affordable and high-quality supplements, as well as promoting awareness about the importance of iron-folic acid supplementation, can significantly contribute to reducing the burden of anaemia and improving overall health outcomes.
Strengths and limitations of the study
The strength of this study lies in the quality of the incorporation of five databases to search for articles. Additionally, we investigated the impact of once-WIFAS on serum ferritin, Hgb, anaemia and academic performance. However, our study is subject to inherent limitations related to the effects of intermittent iron and folic acid supplementation on serum ferritin, Hgb, anaemia, cognitive and school performance, which broadens the scope of the study. The analysis faces challenges owing to the use of various tools and instruments including outcome measurement of mean, median, IQR and SD, particularly for serum ferritin and Hgb complicating comparisons between intervention outcomes. Substantial differences in intervention design, including dose, form of iron supplements, and frequency and duration of supplementation, add complexity. Establishing an optimal dose, frequency or duration for improved or reduced outcomes for school performance remains elusive. There is no trial regarding the effect of WIFAS on mental health. Additionally, the potential influence of other micronutrients remains unclear in some studies. With two studies featuring low-quality studies, the researchers acknowledge the possibility of missing relevant studies.
Conclusion
WIFAS proves effective in enhancing serum ferritin, Hgb concentrations and lowering the risk of anaemia or iron deficiency in adolescents compared with a placebo or no intervention. Moreover, iron supplementation demonstrates positive effects on verbal and nonverbal learning and memory, especially in children with anaemia. Similarly, there are no good enough studies to examine the effect of WIFAS and school performance. Despite these benefits, information on mental health problems, mortality, and potential side effects remains insufficient.
Based on the findings supporting the effectiveness of WIFAS, current recommendations include integrating this intervention into existing school health programmes. Health and education authorities should consider incorporating routine screening for anaemia and providing supplementation to at-risk populations, such as young children. Additionally, healthcare providers and teachers should be trained to counsel patients on the benefits of iron-folic acid supplementation and monitor their adherence to the regimen. Continuous monitoring and evaluation of these programmes are essential to assess their impact and make necessary adjustments to optimise outcomes.
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Ethics statements
Patient consent for publication
References
Footnotes
Contributors The authors’ responsibilities were as follows: SK, BWA and KH: Designed and supervised the study, ensured the quality of the data, and made a substantial contribution to the local implementation of the study and SK, KH, BWA and BM assisted in the analysis and interpretation of the data. All authors critically reviewed the manuscript. SK, the corresponding author did the analysis and drafted the manuscript and had the responsibility to submit the manuscript for publication. SK is responsible for the overall content as the guarantor of the data.
Funding This work was financially supported by Jimma and Werabe University with a reference number of JUIH/IRB/583/2023 and WRU/RP&CS-VP/2023, respectively.
Disclaimer The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.