Molecular epidemiology of Streptococcus agalactiae in non-pregnant populations: a systematic review

Streptococcus agalactiae (group B Streptococcus , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using in silico typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance tetM (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.


Rationale
3 Describe the rationale for the review in the context of existing knowledge.p3 Objectives 4 Provide an explicit statement of the objective(s) or question(s) the review addresses.p3

Eligibility criteria
5 Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.P4, Table S3 Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies.Specify the date when each source was last searched or consulted.
P4, Table S2 Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.P4, Table S2 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
P4-5, Table S3 Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

P4-5
Data items 10a List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.
P3-5, Table S5 10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information.
P3-5, Table S5 Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.
P5, Table S4 Effect measures 12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.NA Synthesis 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and P4

Molecular Epidemiology of Streptococcus agalactiae in non-pregnant populations: A Systematic Review
Luria Leslie Founou Supplementary materials Table S1.PRISMA checklist

Location
where item is reported methods comparing against the planned groups for each synthesis (item #5)).
13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

P4-5
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.P4-5 13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

NA
13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g.subgroup analysis, meta-regression).NA 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.NA

Reporting bias assessment
14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).P4 Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.P4

Study selection 16a
Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
P7-8, Figure 1 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.P7-8, Figure 1 Study characteristics 17 Cite each included study and present its characteristics.P7-8, Table 1, Table S5 Risk of bias in studies 18 Present assessments of risk of bias for each included study.P7-8, Table S4 Results of individual studies 19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.confidence/credible interval), ideally using structured tables or plots.Grand Total (n=7470)

Figure S5 :Figure S6 .
Figure S5: The distribution of isolates by study populations in CC1 clades (A-E).

Table 1
Provide registration information for the review, including register name and registration number, or state that the review was not registered.P424b Indicate where the review protocol can be accessed, or state that a protocol was not prepared.P424c Describe and explain any amendments to information provided at registration or in the protocol.NA Support 25 Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review.P15 DISCUSSIONDiscussion23a Provide a general interpretation of the results in the context of other evidence.P12-15 23b Discuss any limitations of the evidence included in the review.P12-14 From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ 2021;372:n71.doi: 10.1136/bmj.n71For more information, visit: http://www.prisma-statement.org/27 Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.P14

Table S3 : Inclusion and Exclusion Criteria Inclusion criteria
-Studies dealing only with pregnant women and neonates < 3 months -Studies dealing only with prevalence and AST of GBS in pregnant and/or non-pregnant population -Studies published prior 2000 -Non-published papers, -Review, letter to editor, conference paper, case report, -Studies with less than 20 participants or 20 GBS isolates

Table S5 . Overall distribution of sample type from included articles
*Not available: Number of sample positive to GBS were not specified in the study.

Table S8 .
Summary of resistance genes and virulence factors detected in GBS from included articles.

Table S9 .
Description of 9404 GBS isolates used in this study.

Table S10 .
Country wise distribution of 9404 GBS isolates by study populations.