An estimation of global Aeromonas infection prevalence in children with diarrhoea: a systematic review and meta-analysis
BMC Pediatrics volume 23, Article number: 254 (2023)
Diarrhoea is the most commonly related disease caused by Aeromonas. To improve knowledge on prevalence, this systematic review and meta-analysis was performed to evaluate the global prevalence of Aeromonas in children with diarrhoea worldwide.
We systematically searched PubMed, Google scholar, Wiley Online Library, ScienceDirect, and Web of sciences to identify all cross-sectional published papers between 2000 and 10 July 2022. After initial scrutinizing, 31 papers reporting the prevalence of Aeromonas in children with diarrhoea were found to be adequate for meta-analysis. The statistical study was accompanied by using random effects models.
A total of 5660 identified papers, 31 cross-sectional studies encompassing 38,663 participants were included in the meta-analysis. The pooled prevalence of Aeromonas in children with diarrhoea worldwide was 4.2% (95% CI 3.1–5.6%). In the subgroup analysis, the highest prevalence was seen among children in Upper middle-income countries with pooled prevalence of 5.1% (95% CI 2.8–9.2%). The prevalence of Aeromonas in children with diarrhoea was higher in countries with populations of over 100 million people (9.4%; 95% CI 5.6–15.3%), and water and sanitation quality score of less than 25% (8.8%; 95% CI 5.2–14.4%). Additionally, Cumulative Forest Plot showed a decreasing trend in the prevalence of Aeromonas infection in children with diarrhoea over time (P = 0.0001).
The results of this study showed a better comprehension of Aeromonas prevalence in children with diarrhoea on a global scale. As well as our findings showed that much work is still required to decline the burden of bacterial diarrhoea in countries with high populations, low-level income, and unsanitary water.
Diarrhoeal diseases remain a serious worldwide problem among young children. In 2016, diarrhoea was the fifth main cause of fatality among children younger than 5 years, approximately 27% of diarrhoeal deaths occurred among children . Some causes of diarrhoea involve infection by bacteria, viruses, parasites, and other non-infectious causes . Bacteria are responsible for 20–40% of diarrhoea diseases, and various bacterial pathogens have been mostly attributed to diarrhoea episodes, including Escherichia coli, Campylobacter jejuni, Salmonella spp., Yersinia enterocolitica, Vibrio cholerae, Plesiomonas spp, and Aeromonas spp . The rank of Aeromonas vary from first  to fifth  among enteropathogenic bacteria that cause diarrhoea. Childhood diarrhoea is most often caused by Aeromonas species  and in bacteremia disseminated from gastrointestinal tract have mortality rates of 30–70% . Diarrhoea is the common manifestation of Aeromonas infection. Aeromonas has also been related to a variety of extraintestinal presentations. . Aeromonas-associated diarrhoeal is defined as the leading cause of mortality with 1.0 cases per 100,000 . Symptoms of Aeromonas related diarrhoea are quietly changeable, consistency of stool varied from watery to loose to bloody; and diarrhoea is either self-limited, tolerable to one week, or elongated up to two weeks, or become chronic with more than one month period [4, 9]. It is noteworthy that 2,195 children die due to diarrhoea every day, more than malaria, AIDS, and measles combined worldwide . Several investigations have been conducted in many parts of the world at several times to record the prevalence of Aeromonas genus. Anyway, briefed prevalence information of this bacterial disease in diarrhoea children worldwide is needed. Accordingly, the existing study is the first of its kind to specify the pooled prevalence of Aeromons in diarrhoea children on a global scale.
This systematic review and meta-analysis followed PRISMA guidelines (http://www.prisma-statement.org/). A comprehensive literature search was carried out to estimate the prevalence of Aeromonas in children with diarrhoea. Papers were identified using a literature search in five English-language databases (PubMed, Google scholar, Wiley Online Library, ScienceDirect, and Web of sciences) between 2000 and 10 July 2022 using the following keywords: “Aeromonas” “Children” “diarrhoea” alone or in combination with “OR” and/or “AND” operators. Published studies with focused on the epidemiology were selected. All records were imported in Endnote version X8 (Clarivate Analytics, Philadelphia, PA, USA). The limits of language and study group were English and children respectively.
We skimmed titles and abstracts of studies based on determined inclusion and exclusion criteria. The following five inclusion criteria were selected in the current systematic review and meta-analysis: (A) original available full text research papers; (B) studies design been cross-sectional; (C) All papers related to the prevalence of Aeromonas in children with diarrhoea; (D) literatures published in the English language; and (E) Published papers between 2000 and 10 July 2022 were considered. The exclusion criteria were empirical investigations, review papers, clinical trials, letters to the editor, case report articles, unpublished studies, confusing studies, meeting abstracts, congress, case control, cohort studies, and short communication articles.
The data extraction was carried out by 2 members of the research team (HS and SGK) independently from included studies using a pretested format prepared in Microsoft Excel. Following a careful study of fulltext papers, information such as the name of first author, country, year of publication, patients, sample size, type of sample, type of study, prevalence of Aeromonas, and positive samples were exteracted. Any disagreements between the two research team members were resolved by discussion and meeting with a third research team member (AA).
The Newcastle–Ottawa scale was used for assessing the quality of included articles . A score with a most of 10 points was given to each paper according to subject selection (0–5 points), comparability of subjects (0–2 points), and outcome (0–3 points). A total score of 0–4, 5–6, 7–8, and 9–10 points was addressed Unsatisfactory Studies, Satisfactory Studies, Good Studies, and Very Good Studies, respectively .
Data synthesis and statistical analysis
All statistical analysis were carried out using Comprehensive Meta-Analysis (version 3) software. The original papers were explained using forest plot, tables, and figures. Whereof there was heterogeneity among surveys, random effect model was used to evaluate the pooled prevalence. The pooled prevalence of Aeromonas in children with diarrhoea did report globally and was estimated with 95% confidence intervals (CIs). Sub-group analysis included country income level, population, and water and sanitation quality score. The possibility of publication bias was studied using Egger’s regression test and Begg’s test. A meta-regression analysis was carried out to assess the effect of the year of publication on prevalence. Cochrane’s Q test and heterogeneity index (I2 statistics) were used to calculate the amount of heterogeneity among included papers, with I2 values of 25%, 50%, and 75% known as low, moderate, and high heterogeneity, respectively . A P value < 0.05 was considered statistically significant.
Details of prevalence publications
Through online database search, we returned a total of 5660 papers. Review papers on the prevalence of Aeromonas in children with diarrhoea were removed. After the primary check of the titles of eligible papers, related articles to the prevalence of Aeromonas were selected, while irrelevant papers were excluded from the study. Finally, thirty one papers were included in the meta-analysis (Fig. 1) [6, 14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43].
Meta-analysis of Aeromonas prevalence in diarrhoea children
Current survey covered four continents: Europe, Asia, Africa, and South America. No related published papers were found for North, Central America, and Australia. The number of papers included in the meta-analysis was 31, including 38,663 samples, from 2000 to 2022. The principal specifications and outcomes of the included studies are presented in Table 1. Included studies showed high heterogeneity (I2 = 95.27%; p < 0.0001), which is indicative to use random effects model. The pooled prevalence by the random-effects model was 4.2% (95% CI 3.1–5.6%) (Fig. 2). Subgroup analysis showed that regions with populations of over 100 million people had the highest prevalence of Aeromonas (9.4%; 95% CI 5.6–15.3%) (Fig. 3). In addition, the infection was more prevalent in Upper middle-income regions 5.1% (95% CI 2.8–9.2%) (Fig. 4), and regions with water and sanitation quality score of less than 25% (8.8%; 95% CI 5.2–14.4%) (Fig. 5). Our results identify evidence of decreasing Aeromonas infection in children with diarrhoea within the approximately more than two decades covered by reported studies (Fig. 6).
Evaluation of study quality displayed that, among 31 studies, 12 had a total score of 0–4 points (Unsatisfactory Studies), 12 had a total score of 5–6 points (Satisfactory Studies), and 6 had a total score points 7–8 (Good Studies). 1 included study was considered Very Good Studies (Table 2).
As indicated by funnel plot (Fig. 7) asymmetry, no significant publication bias was observed in our study using Eggers regression intercept test (P = 0.98) and Begg and Mazumdar rank correlation (P = 0.13) (Fig. 8a, b). Meta-regression analysis revealed that there was no significant heterogeneity between studies regarding the year of publication (P = 0.08) (Fig. 9).
Enteric bacteria related diarrhoea maintains to be a main cause of morbidity and mortality among children . Troeger et al. , Aeromonas-associated diarrhoeal is known as the leading cause of mortality with 1.0 cases per 100,000 which indicates that children are more sensitive to Aeromonas infection. In humans, Aeromonas is a cause of extra-intestinal and intestinal diseases, particularly in immunocompromised patients, including urinary tract infections, septicemia, wound infections, necrotizing fasciitis, and hepatobiliary tract infections . Clinical symptoms of Aeromonas infection include chronic watery diarrhoea to severe dysentery . Rehydration therapy is sufficient intervention in most children cases of gastroenteritis and watery diarrhoea caused by Aeromonas. Antibiotics are used for only unresponsive and sever cases of Aeromonas gastroenteritis or extraintestinal infections . Correct detection of the genus Aeromonas in laboratory is still a great challenge. Many studies have been conducted with the goal of making detection applied and reproducible, thus increasing the reliability of findings . The current systematic review presents the first published summary of the global prevalence of Aeromonas infection in children with diarrhoea. Based on 31 cross-sectional articles published during the past 22 years, we evaluated the overall prevalence of Aeromonas infection in children with diarrhoea worldwide to be 4.2% (95% CI 3.1–5.6%) using a random effect model. Global prevalence of Aeromonas and its huge burden in some countries such as South Africa, India, and Kenya made Aeromonas reportable disease especially in children with diarrhoea [37, 38, 40]. Prevalence for different studies that met the inclusion criteria of the current review differed largely from 0.002% to 30.5% [21, 35]. Differences in the prevalence of Aeromonas infection in children with diarrhoea reflected possible differences associated with geographic factors in various parts of the world [48, 49], water and sanitation quality, income level, and population densities [50, 51]. In the present study the greatest and lowest prevalence of Aeromonas infection in children with diarrhoea was in India (30.5%)  and Denmark (0.002%) . The pooled prevalence here totally agrees with other investigations of Aeromonas infection in children with diarrhoea, including NASEEM Q N DUBAI (4.1%), and Oliver Waithaka Mbuthia (4.3%) [25, 52]. Furthermore, the pooled prevalence we obtained is approximately in line with the findings of both W S Lee (4.0%) and Saba Talib Hashim (4.0%) [16, 27]. Subgroups analysis based on population, income level, and water and sanitation quality score also was evaluated. Findings show prevalence of Aeromonas in children with diarrhoea being documented from 17 countries that have the higher prevalence in upper middle-income countries 5.1% (95% CI 2.8–9.2%), regions with populations of over 100 million people (9.4%; 95% CI 5.6–15.3%), and water and sanitation quality score of less than 25% (8.8%; 95% CI 5.2–14.4%). The present subgroups analysis confirmed the findings that the high prevalence rate of diarrhoea diseases among children would happen in areas with large population densities, poor water and sanitation facilities , and low-income and middle-income countries . Based on the importance of quality assessment section in meta-analysis getting high-quality studies is crucial in providing reliable and useful results to provide a deeper understanding of research topic. Accordingly, some suggestions for high-quality studies are mentioned as follows:
High-quality research is anchored on a good study question.
High-quality research follows a systematic, relevant study methodology.
High-quality research acknowledges previous studies.
High-quality research uses appropriate, empirical data and correct data analysis methods.
High-quality research is representative and generalizable.
High-quality research has external validity.
High-quality research is replicable and transparent.
Strengths and limitations
This was the first systematic review and meta-analysis to obtain a global prevalence of Aeromonas infection in children with diarrhoea. The comprehensive literature search, duplicated data elicitation, precise methodology, and quality assessment by two autonomous reviewers, obvious exclusion and inclusion criteria, and the lack of publication bias are strengths of this meta-analysis. Nevertheless, there are some limitations that goes back to the nature of the surveys that are as follow: Firstly, most of the investigations included in this meta-analysis did not report information about the virulence genes and antibiotic resistance pattern clearly and consistently; therefore, we were unable to evaluate the effect of these momentous factors. Secondly, the age of patients was not provided clearly in most included studies. Third, in many studies, information about children's gender was not given.
We did provide a systematic review and meta-analysis of Aeromonas infection in children with diarrhoea to get a better comprehension of the global dispensation of this infectious disease. Although diarrhoeal disease fatality has reduced remarkably in the last three decades, lots of work is still required to speed up the decline in the burden of bacterial diarrhoeal diseases in deprived children in terms of safe and healthy water and sanitation, and appropriate health care.
Availability of data and materials
All of the data generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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We sincerely thank staff members of the Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran and Clinical Research Development Unit, Kowsar Hospital, Qazvin University of Medical Sciences, Qazvin, Iran.
This research was funded by the Deputy of Research and Technology, Qazvin University of Medical Sciences, Qazvin, Iran, grant number 401000199.
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran with approval number IR.QUMS.REC.1401.167.
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Sadeghi, H., Alizadeh, A., Vafaie, M. et al. An estimation of global Aeromonas infection prevalence in children with diarrhoea: a systematic review and meta-analysis. BMC Pediatr 23, 254 (2023). https://doi.org/10.1186/s12887-023-04081-3