Review for 10.1186/s12876-025-03634-3 (2025)

Title: Prevalence of Common Diarrheagenic Enterobacteriaceae in Iran (2000-2023): A
Systematic Review and Meta-Analysis
Version: 2 Date: 30 Sep 2024
Reviewer:  Nabi Jomehzadeh
Reviewer's report:
The manuscript undertakes a systematic review and meta-analysis of bacterial gastroenteritis in
Iran. Despite the significance of the topic, the execution is marred by notable methodological
flaws that significantly compromise the validity and reliability of its findings. Consequently,
substantial revisions are imperative before the manuscript can be considered for publication in
a reputable journal.
• The search strategy description lacks sufficient detail. Merely listing keywords without
specifying database-specific search strings, employing precise Boolean operators, setting date
limits (2000-2023 is overly broad), and addressing the inclusion of grey literature, if applicable,
undermines the reproducibility of the search. It is essential to provide a comprehensive, step-by-
step account of the search process in each database, including the number of records retrieved at
each stage. The absence of a PRISMA flow diagram illustrating the selection process from initial
search results to the final included studies is a significant shortcoming. Claiming adherence to
PRISMA guidelines lacks substantiation without a properly completed flow diagram.
• The study selection criteria lack precise definition and operationalization. Terms such
as "precise isolate counts" and "specific provinces or cities" are subjective and open to
interpretation. It is essential to establish specific thresholds for acceptable data quality a priori
and consistently apply them. The absence of a clear definition of "bacterial gastroenteritis"
is a fundamental flaw. It is unclear whether this was based on clinical diagnosis, laboratory
confirmation, or a combination. The specific bacterial species considered should be explicitly
stated. Furthermore, the exclusion of non-English language studies introduces potential
language bias, which needs to be explicitly addressed and justified. Although the methodological
quality assessment using the JBI checklist is mentioned, the absence of its results renders this
crucial step invisible.
• The disproportionate concentration of research studies in central Iran, particularly Tehran,
introduces a notable geographic bias, thus limiting the generalizability of the findings to
the entire country. The authors should conduct a comprehensive evaluation of this bias,
potentially employing statistical methods to adjust for geographic representation in the studies.
Additionally, it is crucial to scrutinize the temporal aspect. Any substantial changes in diagnostic
techniques or healthcare practices during the study period (2000-2023) that could impact the
reported prevalence should be carefully considered and addressed in the analysis.
• The description of the data extraction process is found to be lacking in detail. The absence of
information regarding the assessment of inter-rater reliability, such as the Kappa statistic, gives
rise to concerns about the accuracy and consistency of the data extraction. The approach for
managing missing data is not explicitly stated. While the utilization of random effects modeling
is suitable due to the expected heterogeneity, the authors are required to provide a rationale for
selecting the Der Simonian-Laird method over other potential methods, for example, restricted
maximum likelihood. A comprehensive elucidation of how heterogeneity was evaluated and
managed, including the use of measures such as I², is essential. It is necessary to specify the
statistical software used, including the version and any specific options selected, for instance,
Comprehensive Meta-Analysis.
• It is important to note that relying solely on Begg's test, especially when a non-significant
p-value is obtained, is insufficient for addressing publication bias. A comprehensive approach
includes a visual examination of the funnel plot, with a detailed interpretation that encompasses
any observed asymmetry. Furthermore, it is strongly recommended to conduct further
investigation into publication bias using alternative methods such as Egger's test and the trim-
and-fill method.
• The subgroup analysis should be conducted with greater statistical rigor. Simple descriptive
statistics are insufficient for this purpose. It is essential to employ appropriate statistical tests
such as chi-squared tests, ANOVA, or more sophisticated methods if justified, to compare
prevalence rates across different bacterial species, pathotypes, age groups, and geographic
regions. Additionally, post-hoc tests should be utilized to control for multiple comparisons if
necessary.
• The discussion section predominantly comprises descriptive content that reiterates findings
from individual studies rather than critically synthesizing the meta-analytic results. It is
imperative for the authors to move beyond summarizing individual studies and concentrate
on interpreting the pooled effect sizes, confidence intervals, and measures of heterogeneity.
A comprehensive comparison with existing literature is indispensable, emphasizing both
similarities and discrepancies. Furthermore, the discussion should address the clinical
significance of the findings and their implications for public health policy and future research.
Additionally, a more thorough discussion of the study's limitations, beyond those already
mentioned, is warranted.