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For peer review only

Epidemiology of respiratory bacterial infections in people with lower respiratory tract infections in Africa: The

BARIAFRICA systematic review and meta-analysis protocol

Journal: BMJ Open

Manuscript ID bmjopen-2018-023592

Article Type: Protocol

Date Submitted by the Author: 13-Apr-2018

Complete List of Authors: Tchatchouang, Serges; Centre Pasteur of Cameroon, Department of Virology; Faculty of Sciences, University of Yaoundé I, Department of Biochemistry Bigna, Jean Joel; Centre Pasteur of Cameroon, Department of Epidemiology and Public Health Nzouankeu, Ariane; Centre Pasteur of Cameroon, Department of Bacteriology Penlap, Véronique; Faculty of Sciences, University of Yaoundé I, Department of Biochemistry Fonkoua, Marie-Christine; Centre Pasteur of Cameroon, Department of Bacteriology Ndangang, Marie; Rouen University Hospital, Department of Medical Information and Informatics Kenmoe, Sebastien; Centre Pasteur of Cameroon, Department of Virology Njouom, Richard; Centre Pasteur of Cameroon, Department of Virology

Keywords: Epidemiology < INFECTIOUS DISEASES, Respiratory infections < THORACIC MEDICINE, Epidemiology < THORACIC MEDICINE, Epidemiology < TROPICAL MEDICINE

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Epidemiology of respiratory bacterial infections in people with lower

respiratory tract infections in Africa: The BARIAFRICA systematic review

and meta-analysis protocol

Serges Tchatchouang1, 2

, Jean Joel Bigna3, 4

, Ariane Nzouankeu5, Véronique Penlap

2,

Marie-Christine Fonkoua5, Marie S. Ndangang

6, Sébastien Kenmoe

1, Richard Njouom

1*

1. Department of Virology, Centre Pasteur of Cameroon, Member of the International

Network of Pasteur Institutes, P.O. Box 1274, Yaoundé, Cameroon

2. Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé,

Cameroon

3. Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Member of

the International Network of Pasteur Institutes, P.O. Box 1274, Yaoundé, Cameroon

4. School of Public Health, Faculty of Medicine, University of Paris Sud XI, 63 Rue Gabriel

Péri, 94270, Le Kremlin-Bicêtre, France

5. Department of Bacteriology, Centre Pasteur of Cameroon, Member of the International


6. Department of Medical Information and Informatics, Rouen University Hospital, Rouen,

France

Email addresses: ST ([email protected]), JJB ([email protected]), AN

([email protected]), VP ([email protected]), M-CF (fonkoua@pasteur-

yaounde.org), MSN ([email protected]), SK ([email protected]), RN

([email protected])

* Corresponding author: Department of Virology, Centre Pasteur of Cameroon, Member of

the International Network of Pasteur Institutes, 451 Street 2005, P.O. Box 1274, Yaoundé II,

Yaoundé, Cameroon. E-mail: [email protected]

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Abstract

Introduction

The burden of lower respiratory tract infections (LRTIs) is a substantial public health concern.

However, epidemiology of LRTIs and its main bacterial aetiologies are poorly characterized,

particularly in Africa continent. Providing accurate data can help for designing cost-effective

interventions to curb the burden of respiratory infections in Africa. Therefore, the aim of this

systematic review and meta-analysis, will be to determine the prevalence of respiratory

Bacterial Aetiologies in people with low Respiratory tract Infections in Africa

(BARIAFRICA) and associated factors.

Methods and analysis

We will search PubMed, EMBASE, Web of Science, Africa Journal Online, and Global Index

Medicus to identify cross-sectional studies that reported the prevalence of respiratory bacterial

infections in people with LRTIs in Africa from January 1, 2000 to March 31st, 2018 without

any linguistic restrictions. Diagnosis of respiratory bacterial infections should be based on

polymerase chain reaction and/or culture. Study selection, data extraction, and

methodological quality assessment will be conducted independently by two investigators. The

heterogeneity will be evaluated using the χ² test on Cochrane’s Q statistic. Prevalence will be

pooled using a random-effect meta-analysis model. Subgroup and meta-regression analyses

will be used to identify sources of heterogeneity of prevalence estimates. This study will be

reported according to the Preferred Reporting Items for Systematic reviews and Meta-

Analyses guidelines.

Ethics and dissemination

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Since this study will be based on published data, it does not require ethical approval. This

systematic review and meta-analysis is intended to serve as a basis for determining the burden

of LRTIs, for identifying data gaps and guide future investigations in Africa. The final report

will be published in peer reviewed journals, presented in conferences and submitted to

relevant health policy makers.

Review registration number

PROSPERO, CRD42018092359.

Keywords

Epidemiology; bacteria; lower respiratory tract infections; Africa

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Strengths and limitations of this study

- To the best of our knowledge, this work will be the first systematic review and meta-

analysis reporting the prevalence of respiratory bacterial infection in people with lower

respiratory tract infections in Africa.

- This study will inform and guide policy and practice in decision-making and guide

researchers in future investigations in the field of respiratory bacterial infections.

- At least two review authors will independently assess the study selection, data extraction,

and methodological quality evaluation of included studies.

- The study will be limited by the broad spectrum definition of cases of lower respiratory

tract infection according to the authors of included articles.

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Introduction

Respiratory tract infections are common conditions among humans, with a high burden in

term of public health.1 Depending on their location, diseases can be divided into upper and

lower respiratory tract infections (LRTIs).2 LRTIs include bronchitis, bronchiolitis and

pneumonia 3, are heavy burden and also cause significant economic losses in underdeveloped

countries and especially those in sub-Saharan Africa.4, 5

A systematic analysis in 2015 found

that LRTIs caused 2.74 million deaths and 103 million disability-adjusted life-years (DALYs)

worldwide, making them the fifth leading cause of death overall and the second-leading cause

of DALYs.6 Apart from Asia, the burden of these infections is supported by sub-Saharan

Africa where highest mortalities are among children under 5. For instance, 546.8 and 511.3

deaths per 100 000 were reported in Somalia and Chad respectively meanwhile the lowest

reported mortalities were in Finland in Western Europe with 0.65 deaths per 100 000.6

Several bacteria have been identified as aetiology in the case LRTI including Streptococcus

pneumoniae (pneumococcus), Haemophilus influenzae, Klebsiella pneumoniae,

Staphylococcus aureus, Acinetobacter species, Streptococcus viridans, Pseudomonas

aeruginosa, Escherichia coli, and Proteus species.6, 7

The epidemiology of LTRIs in Africa

can be specific based on its socio-demographical, environmental, and ecological

specificities. A systematic review performed between 2000 and 2015 showed the prevalence

of respiratory pathogens in children under 5 living in Sub-Saharan African countries.8 Apart

from the fact that the systematic review focused only on children, it did not take in account

data from entire Africa, did not perform a meta-analysis, and quality assessment of the

included articles. To the best of our knowledge there is no previous review which assessed

respiratory bacterial aetiologies in people with LRTIs in Africa. We present here a protocol

for a systematic review and meta-analysis to summarise data on the prevalence of respiratory


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(BARIAFRICA), with the aim of providing accurate data for designing cost-effective

interventions to curb the burden of respiratory infections in Africa and guide future research.

Review questions

1. What is the prevalence and distribution of major respiratory bacterial infections among

people with LRTIs living in Africa?

2. What are factors associated with respiratory bacterial infections in people with LRTIs in

Africa?

Method and analysis

Design and registration

This systematic review and meta-analysis protocol will be conducted following Centre for

Reviews and Dissemination guidelines.9 The present BARIAFRICA systematic review and

meta-analysis protocol was reported according to Preferred Reporting Items for Systematic

Reviews and Meta-Analysis Protocols (PRISMA-P).10

The study protocol was registered with


Criteria to consider studies for this review

Inclusion criteria

1. Types of studies: cross-sectional studies.

2. Types of participants: studies conducted in people with LRTIs residing in Africa.

3. Types of outcomes: studies with polymerase chain reaction and bacterial culture used as

tool for the diagnosis respiratory bacterial infections in respiratory samples.

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4. Studies that have been published from January 1, 2000 until March 31st, 2018.

5. Studies published regardless of language of publication.

Exclusion criteria

1. Studies in patients with underlying diseases or conditions like pregnant women.

2. Studies conducted during or after outbreak period.

3. Case reports, letters, conference abstracts, comments, editorials, and case series (< 30

participants).

4. Studies with imported cases of respiratory bacterial infections.

5. In case of duplicates, only the study with the largest sample size will be considered.

6. Studies whose full texts are not available or prevalence data are not complete even after

the request to the authors.

Search strategy for identifying relevant studies

The search strategy including the name of the all African countries and their synonyms will be

applied in electronic databases. The name of the country in the language relevant to that

region will also be applied. Relevant articles will be found by combining the key words in the

field of lower respiratory infections and the names of African sub-regions. The following

databases will be used: PubMed, EMBASE, Web of Science, Africa Journal Online, and

Global Index Medicus. The search strategy in PubMed is presented in the Supplementary

Table 1. The search strategy will be adapted for other databases. The reference list of the

eligible articles and relevant reviews will be manually searched to identify additional studies.

Selection of studies for inclusion in the review

Two review authors using Rayyan application, will independently select records based on the

titles and abstracts. Any disagreement will be solved by consultation and consensus or will

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involve a third review author as an arbitrator. Studies in language different of English or

French will be translated using Google Translate and considered for eligibility. Two review

authors will independently evaluate the full text of the selected records. Discrepancies will be

resolved by consensus or by an arbitration of a third review author. The agreement between

the two first review authors will be estimated by Cohen's kappa coefficient.11

Methodological quality and risk of bias assessment

The evaluation of included studies for methodological quality and bias will be done using an

adapted version of the risk of bias tool for prevalence studies developed by Hoy et al.12

Based

on this tool, studies will be rated as low risk, moderate risk and high risk for scores ≤5, 6–8

and >8, respectively. The defined questions will be scored with 0 for no and 1 for yes. The

total score of each article will be calculated by the sum of its points. Discrepancy of

methodological quality assessment among the review authors will be solved by discussion and

consensus or by arbitration of a third review author.

Data extraction and management

Study characteristics such as name of the first author, year of publication, the study

population, number of bacteria searched, age range, study design, diagnostic criteria and

outcomes measured, location, country in which the study was conducted, criteria for sample

selection and sample size, city, latitude, longitude, altitude, clinical presentation, number of

patients tested, number of patients infected with bacteria, diagnostic technique used, and male

proportion will be recorded. Prevalence will be calculated using primary data on the number

of patients tested and the number of cases for each pathogen searched. Prevalence by country

will be calculated for multinational studies. Where cases and sample for estimating prevalence

will not be available, we will contact the corresponding author of the study to request the

missing information. The countries will be grouped in regions according to the United

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Nations Statistics Division. Lower respiratory infections will be classified as bronchitis,

bronchiolitis and pneumonia. Data extraction will be done independently by two review

authors. Disagreements between the two review authors will be solved by discussion or will

involve if necessary a third review author for arbitration.

Data synthesis

Data will be analysed using the ‘meta’ and ‘metafor’ packages of the statistical software R

(version 3.4.4, The R Foundation for statistical computing, Vienna, Austria). Unadjusted

prevalence will be recalculated based on the information of crude numerators and

denominators provided by individual studies. Prevalence will be reported with theirs 95%

confidence and prediction intervals. To keep the effect of studies with extremely small or

extremely large prevalence estimates on the overall estimate to a minimum, the variance of

the study-specific prevalence will be stabilized with the Freeman-Tukey double arcsine

transformation before pooling the data with the random-effects meta-analysis model.13

Egger’s test will serve for detecting the presence of publication bias.14

A p-value < 0.10 on

Egger test will be considered indicative of statistically significant publication bias.

Heterogeneity will be evaluated by the χ² test on Cochrane’s Q statistic 15

, which will be

quantified by H and I² values. The I² statistic estimates the percentage of total variation across

studies due to true between-study differences rather than chance. In general, I² values greater

than 60-70% indicate the presence of substantial heterogeneity.16

Subgroup analyses will be performed for the following subgroups: children versus adults and

UNSD African Regions. Univariable and multivariable meta-regression analyses will be used

to test for an effect of study and participants’ characteristics (year of publication, seasonality,

number of screened bacteria, age groups, population, UNSD of regions, absolute latitude

[distance to equator], latitude, longitude, and altitude). To be included in multivariable meta-

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regression analysis, a p value < 0.25 in univariable analysis will be required. For categorical

variables, the global p value will be considered for the inclusion in multivariable models. We

will apply a manual backward selection procedure to identify factors independently associated

with the variation of overall prevalence. We successively from the model the less significantly

associated variables. A p value < 0.05 will be considered statistically significant. Following

crude overall prevalence, we will conduct two sensitivity analyses to assess the robustness of

our findings. The first one will include only studies with low risk of bias and the second only

studies reporting data of a full year(s) period (complete season(s)). If it is not possible to

conduct meta-analysis, data will be synthetized using narrative approach.

Potential amendments

We do not plan to make any changes to this protocol. However, if substantial changes occur

during the revision, they will be reported in the published results.

Patient and Public Involvement

Patients and public were not involved in the conception and design of this protocol.


This work relies on published data and therefore does not require an ethical approval. The

findings will be published in a scientific peer-reviewed journal. They will be also submitted to

conferences and to relevant public health actors.

Conclusions

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Taking in account the burden of LRTIs in Africans, the findings from this systematic review

and meta-analysis will be useful for health stakeholders to provide information that can lead

to efficient strategies for controlling the burden of LRTIs in Africa. Different definitions of

LRTIs and inclusion criteria would lead to substantial heterogeneity during meta-analysis.

Authors’ contributions

ST, JJB, SK and RN conceived the protocol and with AN, MSN, VP, and M-CF designed the

protocol. ST, JJB and SK drafted the manuscript. ST, JJB, SK, MSN, AN, VP, M-CF, and RN

revised successive drafts of the manuscript. All authors approved the final version of the

manuscript.

Funding statement

This work received no specific grant from any funding agency in the public, commercial or

not-for-profit sectors

Competing interests statement

The authors declare no competing interest.

References

1. Khan S, Priti S, Ankit S. Bacteria Etiological Agents Causing Lower Respiratory Tract

Infections and Their Resistance Patterns. Iranian biomedical journal 2015; 19(4): 240-6.

2. Neumark T. Treatment of Respiratory Tract Infections in Primary Care with special

emphasis on Acute Otitis Media [Medical Dissertations]. Sweden Linköping University;

2010.

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3. Kocsis B, Szabo D. New treatment options for lower respiratory tract infections.

Expert opinion on pharmacotherapy 2017; 18(13): 1345-55.

4. Organization WH. Estimating the burden of respiratory diseases. Practical Approach

to Lung Health: Manual on Initiating PAL Implementation. Geneva; 2008: 138.

5. Bates M, Mudenda V, Mwaba P, Zumla A. Deaths due to respiratory tract infections in

Africa: a review of autopsy studies. Current opinion in pulmonary medicine 2013; 19(3): 229-

37.

6. Collaborators GL. Estimates of the global, regional, and national morbidity, mortality,

and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for

the Global Burden of Disease Study 2015. The Lancet Infectious diseases 2017; 17(11): 1133-

61.

7. Uzoamaka M, Ngozi O, Johnbull OS, Martin O. Bacterial Etiology of Lower

Respiratory Tract Infections and Their Antimicrobial Susceptibility. Am J Med Sci 2017;

354(5): 471.

8. Armel Moumouni Sanou, Assana Cissé, Tieba Millogo, et al. Systematic Review of

Articles on Etiologies of Acute Respiratory Infections in Children Aged Less Than Five Years

in Sub-Saharan Africa, 2000-2015. EC Microbiology 2016; 3.6: 556-71.

9. Dissemination CfRa. CRD’s guidance for undertaking reviews in healthcare: centers

for reviews and dissemination; 2009.

10. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review

and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews 2015; 4: 1.

11. Viera AJ, Garrett JM. Understanding interobserver agreement: the kappa statistic.

Family medicine 2005; 37(5): 360-3.

12. Hoy D, Brooks P, Woolf A, et al. Assessing risk of bias in prevalence studies:

modification of an existing tool and evidence of interrater agreement. Journal of clinical

epidemiology 2012; 65(9): 934-9.

13. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence.

Journal of epidemiology and community health 2013; 67(11): 974-8.

14. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a

simple, graphical test. BMJ (Clinical research ed) 1997; 315(7109): 629-34.

15. Cochran WG. The Combination of Estimates from Different Experiments. Biometrics

1954; 10(1): 101-29.

16. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in

medicine 2002; 21(11): 1539-58.

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Supplemental Table 1

Search terms

#1 Africa OR Algeria OR Angola OR Benin OR Botswana OR "Burkina Faso" OR Burundi

OR Cameroon OR "Canary Islands" OR "Cape Verde" OR "Central African Republic" OR

Chad OR Comoros OR Congo OR "Democratic Republic of Congo" OR Djibouti OR

Egypt OR "Equatorial Guinea" OR Eritrea OR Ethiopia OR Gabon OR Gambia OR Ghana

OR Guinea OR "Guinea Bissau" OR "Ivory Coast" OR "Cote Ivoire" OR Jamahiriya OR

Kenya OR Lesotho OR Liberia OR Libya OR Madagascar OR Malawi OR Mali OR

Mauritania OR Mauritius OR Mayotte OR Morocco OR Mozambique OR Namibia OR

Niger OR Nigeria OR Principe OR Reunion OR Rwanda OR "Sao Tome" OR Senegal OR

Seychelles OR "Sierra Leone" OR Somalia OR "South Africa" OR "St Helena" OR Sudan

OR Swaziland OR Tanzania OR Togo OR Tunisia OR Uganda OR "Western Sahara" OR

Zaire OR Zambia OR Zimbabwe OR "Central Africa" OR "Central African" OR "West

Africa" OR "West African" OR "Western Africa" OR "Western African" OR "East Africa"

OR "East African" OR "Eastern Africa" OR "Eastern African" OR "North Africa" OR

"North African" OR "Northern Africa" OR "Northern African" OR "South African" OR

"Southern Africa" OR "Southern African" OR "sub Saharan Africa" OR "sub Saharan

African" OR "subSaharan Africa" OR "subSaharan African"

#2 “Lower respiratory tract infect*” OR “lower tract infect*” OR empyema OR bronchiolitis

OR pneumonia OR bronchopneumonia OR Pleuropneumonia OR “severe acute respiratory

tract infect*” OR “severe respiratory tract infect*” OR “acute bronchitis” OR “lung

abscess” OR “pulmonary abscess”

#3 “Streptococcus pneumoniae” OR “S pneumoniae” OR “Pneumococcus” OR

“Streptococcus” OR “Streptococcus pyogenes” OR “Streptococcus viridans”

#4 “Staphylococcus aureus” OR “S aureus” OR “Staphylococcus"

#5 “Haemophilus influenza” OR “Influenza” OR “Haemophilus”

#6 “Klebsiella pneumoniae” OR “K pneumoniae” OR “Klebsiella”

#7 “Escherichia coli” OR “Escherichia”

#8 “Pseudomonas aeruginosa” OR “Pseudomonas”

#9 “Mycoplasma pneumoniae” OR “Mycoplasma” OR “M pneumoniae”

#10 “Coxiella Burnetii” OR “Coxiella”

#11 “Chlamydia psittaci” OR “Chlamydia trachomatis” OR “Chlamydia” OR “Chlamydia

pneumoniae” OR “C pneumoniae” 0R “Chlamidophila pneumoniae”

#12 “Legionella pneumophilia” OR “Legionella longbeachae” OR “Legionella”

#13 “Moraxella catarrhalis” OR “M. catarrhalis ” OR “Branhamella catarrhalis” OR “B

catarrhalis” OR “Moraxella" OR “Branhamella"

#14 “Enterobacter agglomerans” OR “Pantoea agglomerans” OR “Erwinia herbicola” OR

“Enterobacter”

#15 “Bordetella pertussis” OR “pertussis” OR “Bordetella”

#16 “Salmonella"

#17 “Proteus” OR “Flavimonasorzyhabitans” OR “Proteus mirabilis” OR “Proteus vulgaris”

OR “Proteus rettgeri” OR “Proteus penneri” OR “Proteus myxofaciens”

#18 “Acinetobacter” OR “Acinetobacter baumannii” OR “cinetobacter calcoaceticus” OR

“Acinetobacter baumannii-calcoaceticus complex” OR “ABC”

#19 #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14

OR #15 OR #16 OR #17 OR #18

#20 #1 AND #2 AND #19

#21 Limit #20 published 2000/01/01 – 2018/31/03

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PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to

address in a systematic review protocol*

Section and topic Item

No

Checklist item Pages

ADMINISTRATIVE INFORMATION

Title:

Identification 1a Identify the report as a protocol of a systematic review 1

Update 1b If the protocol is for an update of a previous systematic review, identify as such NA

Registration 2 If registered, provide the name of the registry (such as PROSPERO) and registration number 3

Authors:

Contact 3a Provide name, institutional affiliation, e-mail address of all protocol authors; provide physical mailing address of corresponding

author

1

Contributions 3b Describe contributions of protocol authors and identify the guarantor of the review 11

Amendments 4 If the protocol represents an amendment of a previously completed or published protocol, identify as such and list changes;

otherwise, state plan for documenting important protocol amendments

NA

Support:

Sources 5a Indicate sources of financial or other support for the review 11

Sponsor 5b Provide name for the review funder and/or sponsor 11

Role of

sponsor or

funder

5c Describe roles of funder(s), sponsor(s), and/or institution(s), if any, in developing the protocol 11

INTRODUCTION

Rationale 6 Describe the rationale for the review in the context of what is already known 5

Objectives 7 Provide an explicit statement of the question(s) the review will address with reference to participants, interventions, comparators,

and outcomes (PICO)

5-6

METHODS

Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) and report characteristics (such as years

considered, language, publication status) to be used as criteria for eligibility for the review

6-7

Information

sources

9 Describe all intended information sources (such as electronic databases, contact with study authors, trial registers or other grey

literature sources) with planned dates of coverage

7

Search strategy 10 Present draft of search strategy to be used for at least one electronic database, including planned limits, such that it could be

repeated

7-S1

Study records:

Data 11a Describe the mechanism(s) that will be used to manage records and data throughout the review 7-8

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management

Selection

process

11b State the process that will be used for selecting studies (such as two independent reviewers) through each phase of the review (that

is, screening, eligibility and inclusion in meta-analysis)

7-8

Data

collection

process

11c Describe planned method of extracting data from reports (such as piloting forms, done independently, in duplicate), any processes

for obtaining and confirming data from investigators

8-9

Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), any pre-planned data

assumptions and simplifications

8-9

Outcomes and

prioritization

13 List and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, with rationale 8-9

Risk of bias in

individual studies

14 Describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done at the outcome or

study level, or both; state how this information will be used in data synthesis

8

Data synthesis 15a Describe criteria under which study data will be quantitatively synthesised 9-10

15b If data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data and methods of

combining data from studies, including any planned exploration of consistency (such as I2, Kendall’s τ)

9-10

15c Describe any proposed additional analyses (such as sensitivity or subgroup analyses, meta-regression) 9-10

15d If quantitative synthesis is not appropriate, describe the type of summary planned 10

Meta-bias(es) 16 Specify any planned assessment of meta-bias(es) (such as publication bias across studies, selective reporting within studies) 10

Confidence in

cumulative

evidence

17 Describe how the strength of the body of evidence will be assessed (such as GRADE) 9-10

* It is strongly recommended that this checklist be read in conjunction with the PRISMA-P Explanation and Elaboration (cite when available) for important

clarification on the items. Amendments to a review protocol should be tracked and dated. The copyright for PRISMA-P (including checklist) is held by the

PRISMA-P Group and is distributed under a Creative Commons Attribution Licence 4.0.

From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L, PRISMA-P Group. Preferred reporting items for systematic review and

meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;349(jan02 1):g7647.

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Prevalence of respiratory bacterial infections in people with

lower respiratory tract infections in Africa: The BARIAFRICA

systematic review and meta-analysis protocol

Journal: BMJ Open

Manuscript ID bmjopen-2018-023592.R1

Article Type: Protocol

Date Submitted by the Author: 08-Jun-2018

Complete List of Authors: Tchatchouang, Serges; Centre Pasteur of Cameroon, Department of Virology; Faculty of Sciences, University of Yaoundé I, Department of Biochemistry Bigna, Jean Joel; Centre Pasteur of Cameroon, Department of Epidemiology and Public Health Nzouankeu, Ariane; Centre Pasteur of Cameroon, Department of Bacteriology Fonkoua, Marie-Christine; Centre Pasteur of Cameroon, Department of Bacteriology Nansseu, Jobert Richie; Mother and Child Centre, Chantal Biya Foundation, Sickle cell unit Ndangang, Marie; Rouen University Hospital, Department of Medical Information and Informatics Kenmoe, Sebastien; Centre Pasteur of Cameroon, Department of Virology Penlap, Véronique; Faculty of Sciences, University of Yaoundé I, Department of Biochemistry Njouom, Richard; Centre Pasteur of Cameroon, Department of Virology

<b>Primary Subject Heading</b>:

Infectious diseases

Secondary Subject Heading: Epidemiology, Global health, Public health, Respiratory medicine

Keywords: Epidemiology < INFECTIOUS DISEASES, Respiratory infections < THORACIC MEDICINE, Epidemiology < THORACIC MEDICINE, Epidemiology < TROPICAL MEDICINE


BMJ Open on January 30, 2022 by guest. P

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Prevalence of respiratory bacterial infections in people with lower

respiratory tract infections in Africa: The BARIAFRICA systematic review

and meta-analysis protocol

Serges Tchatchouang1, 2, 3

, Jean Joel Bigna4, Ariane Nzouankeu

1, Marie-Christine Fonkoua

1,

Jobert Richie Nansseu5, Marie S. Ndangang

5, Sébastien Kenmoe

2, Véronique B. Penlap

3,

Richard Njouom2*

1. Department of Bacteriology, Centre Pasteur of Cameroon, Member of the International


2. Department of Virology, Centre Pasteur of Cameroon, Member of the International


3. Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé,

Cameroon

4. Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, Member of

the International Network of Pasteur Institutes, P.O. Box 1274, Yaoundé, Cameroon

5. Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of

Yaoundé I, Yaoundé, Cameroon

6. Department of Medical Information and Informatics, Rouen University Hospital, Rouen,

France

Email addresses: ST ([email protected]), JJB ([email protected]), AN

([email protected]), VP ([email protected]), M-CF (fonkoua@pasteur-

yaounde.org), MSN ([email protected]), SK ([email protected]), RN

([email protected])

* Corresponding author: Department of Virology, Centre Pasteur of Cameroon, Member of

the International Network of Pasteur Institutes, 451 Street 2005, P.O. Box 1274, Yaoundé II,

Yaoundé, Cameroon. E-mail: [email protected]

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Abstract

Introduction

The burden of lower respiratory tract infections (LRTIs) is a substantial public health concern.

However, epidemiology of LRTIs and its bacterial aetiologies are poorly characterized,

particularly in the African continent. Providing accurate data can help design cost-effective

interventions to curb the burden of respiratory infections in Africa. Therefore, the aim of this

systematic review and meta-analysis, will be to determine the prevalence of respiratory


(BARIAFRICA) and associated factors.

Methods and analysis

We will search PubMed, EMBASE, Web of Science, Africa Journal Online, CINAHL, and

Global Index Medicus to identify studies that reported the prevalence (of enough data to

compute this estimate) of respiratory bacterial infections in people with LRTIs in Africa from

January 1, 2000 to March 31st, 2018 without any linguistic restrictions. Study selection, data

extraction, and risk of bias assessment will be conducted independently by two investigators.

The heterogeneity will be evaluated using the χ² test on Cochrane’s Q statistic and quantified

with H and I² statistics. Prevalence will be pooled using a random-effect meta-analysis

model. Subgroup and meta-regression analyses will be used to identify sources of

heterogeneity of prevalence estimates. This study will be reported according to the Preferred

Reporting Items for Systematic reviews and Meta-Analyses guidelines.


Since this study will be based on published data, it does not require ethical approval. This

systematic review and meta-analysis is intended to serve as a basis for determining the burden

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of LRTIs, for identifying data gaps and guide future investigations in Africa. The final report

will be published in peer reviewed journals, presented in conferences and submitted to

relevant health policy makers.

Review registration number


Keywords

Epidemiology; bacteria; lower respiratory tract infections; Africa

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Strengths and limitations of this study

- To the best of our knowledge, this work will be the first systematic review and meta-

analysis reporting the prevalence of respiratory bacterial infection in people with lower

respiratory tract infections in Africa.

- This study will inform and guide policy and practice in decision-making and guide

researchers in future investigations in the field of respiratory bacterial infections.

- Two review authors will independently assess the study selection, data extraction, and risk

of bias in included studies.

- The study will be limited by the broad spectrum definition of cases of lower respiratory

tract infection according to the authors of included articles.

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Introduction

Respiratory tract infections are common conditions among humans, with a high burden in

term of public health.1 Depending on their location, diseases can be divided into upper and

lower respiratory tract infections (LRTIs).2 LRTIs including bronchitis, bronchiolitis and

pneumonia3 are heavy burden and also cause significant economic losses in developing

countries and especially those in sub-Saharan Africa.4 5

In sub-Saharan Africa, LRTIs rank at

the third place after HIV/AIDS and malaria in terms of causes of mortality. LTRIs is the first

cause of deaths in 9 African countries.6 A systematic analysis in 2015 found that LRTIs

caused 2.74 million deaths and 103 million disability-adjusted life-years (DALYs) worldwide,

making them the fifth leading cause of death overall and the second-leading cause of

DALYs.7 The burden of these infections is supported by sub-Saharan Africa and Asia where

highest mortality are among children under 5. For instance, 546.8 and 511.3 deaths per

100000 were reported in Somalia and Chad respectively meanwhile the lowest reported

mortality were in Finland in Western Europe with 0.65 deaths per 100000.7 Several bacteria

have been identified as aetiology of LRTIs including Streptococcus pneumoniae

(pneumococcus), Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus,

Acinetobacter species, Streptococcus viridans, Pseudomonas aeruginosa, Escherichia coli,

and Proteus species.7 8

The epidemiology of LTRIs in Africa can be specific based on its

socio-demographical, environmental, and ecological specificities. A systematic review

performed between 2000 and 2015 showed the prevalence of respiratory pathogens in

children under 5 living in Sub-Saharan African countries.9 Apart from the fact that the

systematic review focused only on children, it did not take in account data from entire Africa,

did not perform any meta-analysis of the included studies. To the best of our knowledge there

is no previous review which assessed respiratory bacterial aetiologies in people with LRTIs in

Africa. We present here a protocol for a systematic review and meta-analysis to summarise

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data on the prevalence of respiratory Bacterial Aetiologies in people with low Respiratory

tract Infections in Africa (BARIAFRICA), with the aim to provide accurate data for designing

cost-effective interventions to curb the burden of respiratory infections in Africa and guide

future research.

Review questions

1. What is the prevalence and distribution of respiratory bacterial infections among people

with LRTIs living in Africa?

2. What are sources of heterogeneity of the prevalence of respiratory bacterial infections in

people with LRTIs in Africa?

Method and analysis

Design and registration

This systematic review and meta-analysis protocol will be conducted following Centre for

Reviews and Dissemination guidelines.10

The present BARIAFRICA systematic review and

meta-analysis protocol was reported according to Preferred Reporting Items for Systematic

Reviews and Meta-Analysis Protocols (PRISMA-P).11

The study protocol was registered with


Criteria to consider studies for this review

Inclusion criteria

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1. Types of studies. We will consider cross-sectional studies, case-control studies, baseline

data of cohort studies, surveillance data, as well as control group (without any

intervention) of clinical trials.

2. Types of participants. We will consider studies conducted in people with clinically

diagnosed LRTIs residing in Africa regardless of age group and settings. LRTIs had to be

diagnosed by a physician.

3. Types of outcomes. We will consider studies reporting the prevalence of respiratory

bacterial infections regardless of laboratory diagnostic technique used (or enough data to

compute this estimate). Prevalence will be calculated as number of a respiratory bacterial

infection on number of people with LRTI among which specific bacteria were searched.

4. Studies that have been published from January 1st, 2000 until March 31

st, 2018.

5. Studies published regardless of language of publication.

Exclusion criteria

1. Studies conducted during or after outbreak period.

2. Case reports, letters, conference abstracts, comments, editorials, and case series (< 30

participants).

3. Studies with imported cases of respiratory bacterial infections.

Search strategy for identifying relevant studies

The search strategy including the name of the all African countries and their synonyms will be

applied in electronic databases. The name of the country in the language relevant to that

region will also be applied. Relevant articles will be found by combining the key words in the

field of lower respiratory infections and the names of African sub-regions. The following

databases will be used: Medline through PubMed, EMBASE, Web of Science, CINAHL,

Africa Journal Online, and Global Index Medicus. The search strategy in PubMed is presented

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in the Supplementary Table 1. The search strategy will be adapted for other databases. The

reference list of the eligible articles and relevant reviews will be manually searched to identify

additional studies.

Selection of studies for inclusion in the review

Two review authors using the Rayyan application,12

will independently select records based

on the titles and abstracts. Any disagreement will be solved by discussion and consensus or

will involve a third review author as an arbitrator. Studies in language different of English or

French will be translated using Google Translate and considered for eligibility. Two review

authors will independently evaluate the full text of the selected records. Discrepancies will be

resolved by consensus or by an arbitration of a third review author. The agreement between

the two first review authors will be estimated by Cohen's kappa coefficient.13

Risk of bias assessment

The evaluation of included studies for risk bias will be done using an adapted version of the

risk of bias tool for prevalence studies developed by Hoy et al.14

Based on this tool, studies

will be rated as low risk, moderate risk and high risk for scores ≤5, 6–8 and >8, respectively.

The defined questions will be scored with 0 for no and 1 for yes. The total score of each

article will be calculated by the sum of its points. Discrepancy of risk of bias assessment

among the review authors will be solved by discussion and consensus or by arbitration of a

third review author.

Data extraction and management

Study characteristics such as name of the first author, year of publication, the study

population, number of bacteria searched, age range, study design, setting, diagnostic criteria

and outcomes measured, location, country in which the study was conducted, criteria for

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sample selection and sample size, city, latitude, longitude, altitude, clinical presentation,

number of clinical isolates, comorbid conditions/underlying conditions, number of patients

tested, number of patients infected with bacteria, diagnostic technique used, and male

proportion will be recorded. Prevalence by country will be calculated for multinational

studies. Where cases and sample for estimating prevalence will not be available, we will

contact the corresponding author of the study to request the missing information. The

countries will be grouped in regions according to the United Nations Statistics

Division. Lower respiratory infections will be classified as bronchitis, bronchiolitis and

pneumonia. Data extraction will be done independently by two review authors. Disagreements

between the two review authors will be solved by discussion or will involve if necessary a

third review author for arbitration.

Data synthesis

Data will be analysed using the ‘meta’ and ‘metafor’ packages of the statistical software R

(version 3.4.4, The R Foundation for statistical computing, Vienna, Austria). Unadjusted

prevalence will be recalculated based on the information of crude numerators and

denominators provided by individual studies. Prevalence will be reported with theirs 95%

confidence and prediction intervals. To keep the effect of studies with extremely small or

extremely large prevalence estimates on the overall estimate to a minimum, the variance of

the study-specific prevalence will be stabilized with the Freeman-Tukey double arcsine

transformation before pooling the data with the random-effects meta-analysis model.15

Only

studies conducted in populations with close clinical presentation/underlying conditions and

with same laboratory diagnostic technique will be pooled together. If it is not possible to

conduct meta-analysis, data will be synthetized using a narrative approach. Egger’s test will

serve for detecting the presence of publication bias.16

A p-value < 0.10 on Egger test will be

considered indicative of statistically significant publication bias. Heterogeneity will be

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evaluated by the χ² test on Cochrane’s Q statistic 17

, which will be quantified by H and I²

values. The I² statistic estimates the percentage of total variation across studies due to true

between-study differences rather than chance. In general, I² values greater than 60-70%

indicate the presence of substantial heterogeneity.18

In the case of substantial heterogeneity, subgroup and meta-regression analyses will be used

to investigate sources of heterogeneity. Subgroup analyses will be performed for the

following subgroups: children versus adults, UNSD African Regions, level of country

income, clinical presentation, setting (primary care, intensive care and emergency units,

inpatients, outpatients) and study period of inclusion. Univariable and multivariable meta-

regression analyses will be used to test for an effect of study and participants’ characteristics

(year of publication, seasonality, setting, clinical presentation, comorbid conditions, number

of screened bacteria, age groups, population, UNSD of regions, absolute latitude [distance to

equator], latitude, longitude, and altitude). To be included in multivariable meta-regression

analysis, a p value < 0.25 in univariable analysis will be required. For categorical variables,

the global p value will be considered for the inclusion in multivariable models. We will apply

a manual forward selection procedure to identify factors independently associated with the

variation of the overall prevalence. We will successively add in the model the more

significantly associated variables. The final model that will be considered is the one with

lowest Bayesian Information Criterion. A p value < 0.05 will be considered statistically

significant. Following crude overall prevalence, we will conduct two sensitivity analyses to

assess the robustness of our findings. The first one will include only studies with low risk of

bias and the second only studies reporting data of a full year(s) period (complete season(s)).

Potential amendments

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We do not plan to make any changes to this protocol. However, if substantial changes occur

during the review, they will be reported in the published results.

Patient and Public Involvement

Patients and public were not involved in the conception and design of this protocol.


This work relies on published data and therefore does not require an ethical approval. The

findings will be published in a scientific peer-reviewed journal. They will be also submitted to

conferences and to relevant public health actors.

Conclusions

Taking in account the burden of LRTIs in Africans, the findings from this systematic review

and meta-analysis will be useful for health stakeholders to provide information that can lead

to efficient strategies for controlling the burden of LRTIs in Africa. As all settings in Africa

are not able to diagnose bacterial aetiologies in people with LRTI, knowledge of major

respiratory bacterial infections can help in this case to orientate the first line treatment.

Different definitions of LRTIs and inclusion criteria would lead to substantial heterogeneity

during meta-analysis.

Authors’ contributions

ST, JJB, SK and RN conceived the protocol and with AN, MSN, VP, and M-CF designed the

protocol. ST, JJB and SK drafted the manuscript. ST, JJB, SK, MSN, AN, VP, M-CF, and RN

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revised successive drafts of the manuscript. All authors approved the final version of the

manuscript.

Funding statement

This work received no specific grant from any funding agency in the public, commercial or

not-for-profit sectors

Competing interests statement

The authors declare no competing interest.

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Supplemental Table 1

Search terms

#1 Africa OR Algeria OR Angola OR Benin OR Botswana OR "Burkina Faso" OR Burundi

OR Cameroon OR "Canary Islands" OR "Cape Verde" OR "Central African Republic" OR

Chad OR Comoros OR Congo OR "Democratic Republic of Congo" OR Djibouti OR

Egypt OR "Equatorial Guinea" OR Eritrea OR Ethiopia OR Gabon OR Gambia OR Ghana

OR Guinea OR "Guinea Bissau" OR "Ivory Coast" OR "Cote Ivoire" OR Jamahiriya OR

Kenya OR Lesotho OR Liberia OR Libya OR Madagascar OR Malawi OR Mali OR

Mauritania OR Mauritius OR Mayotte OR Morocco OR Mozambique OR Namibia OR

Niger OR Nigeria OR Principe OR Reunion OR Rwanda OR "Sao Tome" OR Senegal OR

Seychelles OR "Sierra Leone" OR Somalia OR "South Africa" OR "St Helena" OR Sudan

OR Swaziland OR Tanzania OR Togo OR Tunisia OR Uganda OR "Western Sahara" OR

Zaire OR Zambia OR Zimbabwe OR "Central Africa" OR "Central African" OR "West

Africa" OR "West African" OR "Western Africa" OR "Western African" OR "East Africa"

OR "East African" OR "Eastern Africa" OR "Eastern African" OR "North Africa" OR

"North African" OR "Northern Africa" OR "Northern African" OR "South African" OR

"Southern Africa" OR "Southern African" OR "sub Saharan Africa" OR "sub Saharan

African" OR "subSaharan Africa" OR "subSaharan African"

#2 “Lower respiratory tract infect*” OR “lower tract infect*” OR empyema OR bronchiolitis

OR pneumonia OR bronchopneumonia OR Pleuropneumonia OR “severe acute respiratory

tract infect*” OR “severe respiratory tract infect*” OR “acute bronchitis” OR “lung

abscess” OR “pulmonary abscess”

#3 “Streptococcus pneumoniae” OR “S pneumoniae” OR “Pneumococcus” OR

“Streptococcus” OR “Streptococcus pyogenes” OR “Streptococcus viridans”

#4 “Staphylococcus aureus” OR “S aureus” OR “Staphylococcus"

#5 “Haemophilus influenza” OR “Influenza” OR “Haemophilus”

#6 “Klebsiella pneumoniae” OR “K pneumoniae” OR “Klebsiella”

#7 “Escherichia coli” OR “Escherichia”

#8 “Pseudomonas aeruginosa” OR “Pseudomonas”

#9 “Mycoplasma pneumoniae” OR “Mycoplasma” OR “M pneumoniae”

#10 “Coxiella Burnetii” OR “Coxiella”

#11 “Chlamydia psittaci” OR “Chlamydia trachomatis” OR “Chlamydia” OR “Chlamydia

pneumoniae” OR “C pneumoniae” 0R “Chlamidophila pneumoniae”

#12 “Legionella pneumophilia” OR “Legionella longbeachae” OR “Legionella”

#13 “Moraxella catarrhalis” OR “M. catarrhalis ” OR “Branhamella catarrhalis” OR “B

catarrhalis” OR “Moraxella" OR “Branhamella"

#14 “Enterobacter agglomerans” OR “Pantoea agglomerans” OR “Erwinia herbicola” OR

“Enterobacter”

#15 “Bordetella pertussis” OR “pertussis” OR “Bordetella”

#16 “Salmonella"

#17 “Proteus” OR “Flavimonasorzyhabitans” OR “Proteus mirabilis” OR “Proteus vulgaris”

OR “Proteus rettgeri” OR “Proteus penneri” OR “Proteus myxofaciens”

#18 “Acinetobacter” OR “Acinetobacter baumannii” OR “cinetobacter calcoaceticus” OR

“Acinetobacter baumannii-calcoaceticus complex” OR “ABC”

#19 #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR

#14 OR #15 OR #16 OR #17 OR #18

#20 #1 AND #19

#21 Limit #20 published 2000/01/01 – 2018/05/31

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PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to

address in a systematic review protocol*

Section and topic Item

No

Checklist item Pages

ADMINISTRATIVE INFORMATION

Title:

Identification 1a Identify the report as a protocol of a systematic review 1

Update 1b If the protocol is for an update of a previous systematic review, identify as such NA

Registration 2 If registered, provide the name of the registry (such as PROSPERO) and registration number 3

Authors:

Contact 3a Provide name, institutional affiliation, e-mail address of all protocol authors; provide physical mailing address of corresponding

author

1

Contributions 3b Describe contributions of protocol authors and identify the guarantor of the review 11

Amendments 4 If the protocol represents an amendment of a previously completed or published protocol, identify as such and list changes;

otherwise, state plan for documenting important protocol amendments

NA

Support:

Sources 5a Indicate sources of financial or other support for the review 11

Sponsor 5b Provide name for the review funder and/or sponsor 11

Role of

sponsor or

funder

5c Describe roles of funder(s), sponsor(s), and/or institution(s), if any, in developing the protocol 11

INTRODUCTION

Rationale 6 Describe the rationale for the review in the context of what is already known 5

Objectives 7 Provide an explicit statement of the question(s) the review will address with reference to participants, interventions, comparators,

and outcomes (PICO)

5-6

METHODS

Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) and report characteristics (such as years

considered, language, publication status) to be used as criteria for eligibility for the review

6-7

Information

sources

9 Describe all intended information sources (such as electronic databases, contact with study authors, trial registers or other grey

literature sources) with planned dates of coverage

7

Search strategy 10 Present draft of search strategy to be used for at least one electronic database, including planned limits, such that it could be

repeated

7-S1

Study records:

Data 11a Describe the mechanism(s) that will be used to manage records and data throughout the review 7-8

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management

Selection

process

11b State the process that will be used for selecting studies (such as two independent reviewers) through each phase of the review (that

is, screening, eligibility and inclusion in meta-analysis)

7-8

Data

collection

process

11c Describe planned method of extracting data from reports (such as piloting forms, done independently, in duplicate), any processes

for obtaining and confirming data from investigators

8-9

Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), any pre-planned data

assumptions and simplifications

8-9

Outcomes and

prioritization

13 List and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, with rationale 8-9

Risk of bias in

individual studies

14 Describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done at the outcome or

study level, or both; state how this information will be used in data synthesis

8

Data synthesis 15a Describe criteria under which study data will be quantitatively synthesised 9-10

15b If data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data and methods of

combining data from studies, including any planned exploration of consistency (such as I2, Kendall’s τ)

9-10

15c Describe any proposed additional analyses (such as sensitivity or subgroup analyses, meta-regression) 9-10

15d If quantitative synthesis is not appropriate, describe the type of summary planned 10

Meta-bias(es) 16 Specify any planned assessment of meta-bias(es) (such as publication bias across studies, selective reporting within studies) 10

Confidence in

cumulative

evidence

17 Describe how the strength of the body of evidence will be assessed (such as GRADE) 9-10

* It is strongly recommended that this checklist be read in conjunction with the PRISMA-P Explanation and Elaboration (cite when available) for important

clarification on the items. Amendments to a review protocol should be tracked and dated. The copyright for PRISMA-P (including checklist) is held by the

PRISMA-P Group and is distributed under a Creative Commons Attribution Licence 4.0.

From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L, PRISMA-P Group. Preferred reporting items for systematic review and

meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;349(jan02 1):g7647.

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