{'fraction_non_alphanumeric': 0.021511553683135454, 'fraction_numerical': 0.01078769309332312, 'mean_word_length': 5.12470680218921, 'pattern_counts': {'":': 0, '<': 2, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Incidence and prevalence of type 1 diabetes in Africa: a systematic review and meta-analysis protocol

Introduction Type 1 diabetes is reported to have significant mortality in Africa. However, there is a paucity of data on pooled estimates of its incidence and prevalence in Africa. This first systematic review and meta-analysis will be conducted to determine the incidence and prevalence of this condition in Africa. Methods Based on predefined criteria, electronic databases, including PubMed, Excerpta Medica database, Africa Journal Online and Web of Science, will be searched for relevant studies involving paediatric and adult patients, with no language restrictions. Quality assessment of the individual studies will be performed, and the Q-statistic test and I2 statistic test will be used to assess statistical heterogeneity. Appropriate meta-analysis will then be used to pool studies judged to be clinically homogenous. Egger’s test will be used to detect publication bias. The planned search dates for the eligible articles are from 1 September to 30 September 2022. Ethics and dissemination Since this review will use previously published studies, it will not require the consent of an ethics committee. The results will be prepared and disseminated through a peer-reviewed journal and will be presented in relevant conferences. PROSPERO registration number CRD42021278227.


INTRODUCTION
The true epidemiological feature of type 1 diabetes is unknown in Africa despite recent reports suggesting an increase in the number of persons with the condition in the continent. 1 2 In 2013, the International Diabetes Federation (IDF) reported that about 39 000 individuals were living with type 1 diabetes in Africa, with an incidence of 6.4/1 000 000 among those less than 14 years old. 3 In 2017, the IDF reported an estimated 50 600 children and adolescents below 20 years living with type 1 diabetes in Africa. 4 Interestingly, these IDF reports are limited to a cohort of subjects aged less than 20 years old. It is therefore necessary to provide supplementary data on type 1 diabetes in all age categories in Africa.
A previous narrative review of some early population-based studies across different countries in Africa stated that the prevalence of type 1 diabetes was <1/1000, with incidence rates ranging from 1.5 to 10.1/100 000 per year. 5 This was not a systematic review and only presented results in ranges, reporting conflicting findings regarding the prevalence of type 1 diabetes in sex-specific groups across east to west Africa. Type 1 diabetes is reported to have high mortality in Africa. It stands out as an almost neglected disease in the continent, receiving very little scientific attention and funding for research. 1 A possible reason for this neglect is the high cost of confirmatory diagnostic tests for type 1 diabetes (dosage of islet autoantibodies), potentially underestimating true prevalence estimates. Therefore, in this context, there is a need for accurate, evidencebased epidemiological data summarising the trends of the condition, which may serve as a basis for developing adequate public health strategies, health service organisations and interventions in the African continent. 6 To our knowledge, this is the first systematic review and meta-analysis aiming to summarise available data on the incidence and prevalence of type 1 diabetes in Africa. We will also STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ We will employ robust methods and statistical analyses to determine the burden of type 1 diabetes mellitus, providing evidence for public health strategies. ⇒ The review will include primary studies without language restrictions, allowing the maximum inclusion of studies published on the topic. ⇒ The review uses an inclusive search in large databases, with a long-time range. ⇒ Methodological biases in the primary studies included may cause uncertainty in the final results obtained. ⇒ This study will also assess the quality of published incidence and prevalence data of type 1 diabetes in Africa.
Open access examine the epidemiology of the condition with regard to age, sex, geographical region and temporal trends. The findings of this study are intended to serve as a supplement to the recent IDF atlas reports on the incidence and prevalence of type 1 diabetes in Africa. While the results of the IDF are based on a single study per African country available and are limited to data in the 0-20 years age group, this study will aim to provide estimates using multiple studies available per given African country, and also inform on epidemiological estimates of type 1 diabetes in adults aged 20 years and above.

REVIEW QUESTION
What are the epidemiological features of type 1 diabetes on the African continent?

OBJECTIVES
The objective of the present systematic review and metaanalysis is to estimate the prevalence and incidence of type 1 diabetes in patients (of any age, including paediatrics or adults) in Africa.
Secondary objectives 1. Assess the quality of published incidence and prevalence data of type 1 diabetes in Africa. 2. Estimate the incidence and prevalence of type 1 diabetes by gender, age and geographical delimitations. 3. Determine the temporal trend of the prevalence and incidence of type 1 diabetes in Africa. 4. Compare incidence and prevalence of type 1 diabetes between North Africa and sub-Saharan Africa.

METHODS AND DESIGN
The Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) guidelines served as the template for reporting this protocol. 7 This systematic review and meta-analysis will be conducted as recommended in the Joanna Briggs Institute (JBI) reviewer's manual for prevalence and incidence review. 8 The PRISMA-P checklist is attached (see online supplemental file 1).

Patient and public involvement
Patients and the public will not be involved in the design or planning of the study.
Criteria for considering studies for the review Types of studies This study shall select all hospital-based and populationbased observational studies that correctly provide data estimates on the incidence and prevalence of type 1 diabetes in Africa. These observational studies will include population-based cross-sectional studies for estimating the prevalence and prospective, population-based cohort studies for estimating the incidence.

Population
We will consider studies involving children, adolescents and adults with no particular age limit with a clinical diagnosis of type 1 diabetes. This refers to all children/ adolescents/adults with diabetes on insulin therapy, and confirmed by the treating physician as 'type 1 diabetes'.

Outcome
Studies included in this review will be studies reporting on the prevalence and/or incidence of type 1 diabetes or insulin dependent diabetes mellitus (IDDM) or juvenile diabetes conducted in Africa. Studies lacking explicit method descriptions will be excluded if the information was not provided after contacting authors twice. The minimum acceptable sample size for the preliminary studies is 30 participants from the general population. This is to ensure that we recruit studies with large sample sizes, in order to provide accurate estimates on type 1 diabetes incidence and prevalence.

Research strategy for identifying relevant studies
The search strategy will be conducted as discussed below.

Bibliographic database searches
A comprehensive search of PubMed, Excerpta Medica database, Africa Journal Online and Web of Science will be conducted to identify all published relevant articles without any language and period of publication restriction. A search strategy based on the combination of relevant terms will be designed and applied. This search strategy was built according to PRESS guidelines. 9 The primary search strategy in PubMed is shown in online supplemental file 2. This search strategy will be adapted for search in other databases. The search strategy will be applied in all databases on 3 January 2022. A manual search consisting of scanning reference lists of eligible studies and relevant reviews will be performed to identify missed studies during the review process or by search strategy or for studies not indexed in the five targeted electronic databases. For articles published in a language other than English and French, an experienced translator in the concerned language will be contacted for translation. Studies published from 1 January 1980 to 31 December 2021 will be deemed eligible for assessment.

Searching for other sources
We will scan the references of all selected articles for additional data sources missed during our search, and their full texts obtained. All studies that meet our selection criteria will be included for analyses.
Selection of studies to include in the review Two investigators (JCK and JJB) will independently screen records for eligibility based on titles and abstracts. Full texts of articles deemed potentially eligible will be retrieved. Further, these investigators will independently assess the full text of each study for eligibility and consensually retained studies to be included. Disagreements will be resolved by consensus and following an Open access independent review by a third reviewer in case of unresolved disagreements.

Data extraction and management
Data will be extracted using a preconceived, piloted and standardised data abstraction form. Two investigators (JCK and BBA) will independently extract data, including the name of the first author, year of publication, study design, period of inclusion of participants, recruitment site (country, number of locations), sampling method, sample size, number of cases, age distribution, proportion male and presence of specific conditions/disease. After article extraction and data collection, the authors will unanimously decide if it is necessary to implement the study protocol, if the data appears to be limited.

Methodological quality assessment
We will use an adapted version of the tool developed by the JBI to assess the risk of bias in included studies. 8 All selected full-text articles will be critically appraised by two investigators after comparing it to the nine elements found in the JBI checklist for studies reporting prevalence data. Any unanimous decision by the both investigators on article inclusion/exclusion on the basis of quality is final, with a third investigator needed, in case of any decision discrepancy (CAD).

Data synthesis and analysis
Meta-analyses will be conducted using the meta packages of the R statistical software (V.3.6.0, The R Foundation for Statistical Computing, Vienna, Austria). Only populations with the same clinical profile (specific disease or condition) will be pooled together. The aim of pooling data from patients/population with the same clinical profile is to reduce clinical heterogeneity. With metaprop function, we will use the reference method to synthesise prevalence data as recommended by Barendregt and colleagues. 10 All prevalence estimates will be reported with their 95% CI; alongside their 95% prediction intervals that can help better understand the uncertainty. 11 The prediction interval predicts the range in which a future individual observation will fall, while the CI will show the likely range of values associated with a statistical parameter of the epidemiological data of interest. To minimise the effect of studies with extremely small or extremely large prevalence estimates on the overall estimate, the variance of study-specific prevalence will be stabilised with the Freeman-Tukey double arcsine transformation before pooling the data with the random effects meta-analysis model. 10 Heterogeneity will be assessed by the χ² test on Cochrane's Q statistic, 12 and quantified by I² values, assuming I² values of 25%, 50% and 75%, representing low, medium and high heterogeneity. 13 The Egger test will be used to assess the presence of publication bias. 14 A p value <0.10 will be considered indicative of a statistically significant publication bias. 15 It was decided a priori that if publication bias were present, it would not be adjusted for since we believed that the prevalence estimates of interest would likely be published even if substantially different from previously reported estimates. We will conduct subgroup analyses according to subregions in Africa (Northern, Southern, Western, Central and Eastern), level of country human development index, age group and sex. We will calculate R² through meta-regression analysis (with metareg function) to identify covariates that explain the heterogeneity in the overall estimate and quantify the heterogeneity. Inter-rater agreements between investigators for study inclusion and methodological quality assessment will be assessed using Cohen's κ.

Presentation and reporting of results
The study selection process will be summarised using a flow diagram. Quantitative data will be presented in tables of individual studies and in summary tables or forest plots where appropriate. The quality scores of bias for each eligible study will be reported accordingly.

Potential study amendments
We do not plan to modify the protocol to avoid reporting bias. However, if necessary, any amendment in the review process will be reported for transparency.

Ethics and dissemination
Since primary data will not be collected in this study, ethical approval is not required. This review is expected to provide accurate data on the incidence and prevalence of type 1 diabetes in Africa. The final report will be published in an international peer-reviewed journal.
Contributors JCK and ES developed the idea, design for this protocol. JCK, BBA, CAD wrote the first draft of the manuscript. CAD and JJB developed the search strategy. All authors critically revised this manuscript. JCK and ES are the guarantors of the review. All authors critically revised the methodology and intellectual content and approved the final version of this manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
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.

Patient consent for publication Not applicable.
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.
Open access 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/.