Vancomycin Resistance Enterococcus in Africa in Onehealth approach: A systematic review and meta-analysis

Background Vancomycin resistance enterococci are enterococci that cannot be cured with vancomycin treatment. To combat this resistance, an integrated disciplinary action is mandatory. Therefore, this study aimed to show the prevalence of these agents with the concept of one health approach. Methods Literature search was conducted on PubMed, Google scholar and Hinari with the term “Vancomycin resistance enterococcus in Africa” in august 1-3, 2019. All available articles exported to “Endnote version 7.1” then to Microsoft word. All the articles checked to meet our criteria for the review. Those articles reported the prevalence of vancomycin resistance Enterococcus and published from 2010 to present in the English language was included for the review. There were 151 articles from the databases; of this, 37 articles included after extensive review with two independent authors. Result Out of 4112 samples collected, 1527 isolates identified with overall magnitude of VRE as 28.8% (12.9%-44.7%) in Africa with a one-health perspective. The meta-analysis indicates that there was substantial heterogeneity among the articles with consistency index (I 2 ) =99.9%. A higher rate of Vancomycin resistance enterococci was identified from South Africa 74.8%, followed by Egypt 37. 2%. Laboratory method employed for identification showed that a higher rate was from BacTec 98.8%, followed by PCR 59.2%. It is also a non-human sample source was with higher rates of VRE i.e. 32.5%. Conclusion This meta-analysis indicates there was a high rate of Vancomycin resistance enterococcus in African continent. A lot should be done to prevent and control the transmition of this resistance gene circulating in the environment.

Introduction vancomycin-resistant enterococci an enterococci (VRE) that acquired resistance to the antibiotic vancomycin used to treat infection caused by these bacteria [1]. VRE emerged as important nosocomial pathogens since 1987, and there is concern that they may be, or become, endemic in the non-hospital setting, both in human and animal carriers and in the general environment [2]. It advanced to inoffensive colonizer of the gut of humans and animals, ranging from insects to reptiles, birds, and mammals. Whilst they are ubiquitous, they represent a minority population of the healthy human microbiome [3]. Outside the gut, they can disseminate in the environment where they survive in wastewater, slurry and soil contaminated by manure and hence used as indicators of faecal contamination in recreational or drinking water [4].
Members of the genus Enterococcus are well-documented pathogens associated with various clinical manifestations, including bacteremia, infective endocarditis, intraabdominal and pelvic infections, urinary tract infections, and, in rare cases, central nervous system infections [5][6][7]. Infection with VREs associated with an increased mortality rate, illustrated by a 2.5-fold increase in mortality for patients suffering from VRE bacteremia [8].
The 'One Health' concept recognizes that the health of people connected to the health of animals and the environment. Humans, animals, plants, food of animal origin and our environment all potentially constitute overlapping reservoirs of antimicrobial resistance (AMR). Given the serious health threat, a common understanding of AMR, and of the need for a One Health approach to tackle it, are of fundamental importance [9]. VRE is one of this multidrug resistance that needs comprehensive data that indicates the magnitude of VRE in Africa. Therefore, the aim of this study was to compile available data of vancomycin resistance enterococci in Africa in one health perspective. Methods 4 Literature Search Strategy A literature search conducted on PubMed, Google scholar and Hinari with the term "Vancomycin resistance enterococcus in Africa" in august 1-3, 2019. All available articles exported to "Endnote version 7.1" then to Microsoft word. All the articles checked to meet our criteria for the review. Those articles reported the prevalence of vancomycin resistance Enterococcus and published from 2010 to present in the English language was included for the review. There were 151 articles from the databases; of this, 37 articles included after extensive review with two independent authors. Articles failed to fulfill the criteria excluded as presented in Figure 1 according to the PRISMA protocol 2015.

Data analysis
Excel used for data extraction and then exported to Microsoft word as presented in table 1. Meta-analysis was conducted with OpenMeta analyst software available freely and the result presented as a forest plot in Figure 2 &3 and in Table 2.

Data Quality
The quality of the study included in the review and meta-analysis evaluated with 14 points scoring tool. NIH quality assessment tool for observational and cross-sectional studies in which studies categorized as a good, fair and poor quality based on the internal validity of each article[10].

Heterogeneity and Publication Bias
The heterogeneity of the publication was determined according to the measure of the inconsistency index (I 2 ). That measures the total variations in the articles was due to heterogeneity rather than by chance with a value of <30%, 30-60%, 61-75% and >75% suggestive of low, moderate, substantial and considerable heterogeneity, respectively [11] . No need for conducting publication bias as the study is considerably heterogeneous 5 as recommended by Hak T. et al [12].

Study features
As presented in table 1 studies that conducted in African countries that reported the prevalence of enterococcus and resistance rate for vancomycin, published after 2010.
Whatever the sample type and laboratory method employed captured for the review and meta-analysis. The author name, year of publication, country of origin, source of sample (human vs non-human), laboratory method used (culture & polymerase chain reaction (PCR), PCR only, BacTec, culture only, number of enterococcus isolated and the proportion of vancomycin resistance enterococci isolated was extracted from each articles.

Country of origin for the articles
The country in which the articles originated is indicated as follows, eight (8)

Results
The magnitude of vancomycin resistance Enterococci Out of 4112 samples collected, 1527 isolates identified with overall magnitude of VRE 28.8% (12.9%-44.7%) in Africa in a one-health perspective. The meta-analysis indicates that there was substantial heterogeneity among the articles with a consistency index (I 2 ) = 99.9%.

Subgroup analysis
Country level 6 The subgroup analysis performed at country level indicates that a high rate of VRE in South Africa 74.8% and the least was from Algeria and Nigeria 2.8% each even if only one article captured from Algeria as presented in Figure 2.

Laboratory method
Subgroup analysis of VRE based on the laboratory method in presented in Table 2 that grouped into culture & polymerase chain reaction (PCR), PCR only, BacTec, culture only. It indicates that the highest rates of VRE even if a single study conducted using BacTec was 98.8 %, followed by using only PCR 59.2%, that conducted using both culture & PCR 38.9% and identified using culture only 7.3 %, chronologically.

Sample Source
As tried to present in Figure 3 subgroup analysis based on the source of sample conducted by categorizing as non-human and human source. It indicates that a higher rate of VRE was detected from non-human sample sources 32.5% vs 23.3 % human source.

Discussion
Vancomycin is one of the few antibiotics that can be used to treat infections resulting from Gram-positive multidrug-resistant organisms (MDRO) including such as enterococci [49]. In the late 1980s, the emergence of VRE in European hospitals and the isolation of a few years later of VRE from Danish raw minced pork and frozen poultry generated global concern [50]. One Health is the concept that the optimum health for people, animals and the environment can best ensured through the ongoing cooperative efforts of scientists and practitioners in a variety of discipline [51].
Our study based on data available in Africa on VRE in one health perspective in which animal, human, avian and environmental source of samples analyzed to determine the pooled prevalence of VRE. The overall prevalence of VRE was 28.8 % in Africa from 7 different sample source in a one-health approach. Which is higher than study systematic review and meta-analysis which was conducted in Iran that is 14 % VRE [52]. This difference may be due to the source of the sample we used for the analysis is from different sources. The high rates of this VRE are may be due to the nature of enterococci, which is highly resistant for environmental conditions and different antibiotics [53,54].
There is no data of systematic review and meta-analysis from other parts of the world including Africa to compare and contrast more with our finding, but the subgroup analysis at country level showed that there is a pronounced difference of VRE in different countries, which ranged from 74.8 % from South Africa to 2.8 % in Algeria.
Our study also performed a subgroup meta-analysis based on the laboratory method used for isolation and identification of Enterococcus & VRE. It showed that the higher the technique used the more sensitive for detection of VRE in which studies conducted with BacTec and PCR leads for isolation of more VRE, whereas those conducted with conventional culture less likely detect VRE. Some studies reported in comparison of PCR and Culture indicates that PCR is more sensitive and specific than later [55,56].
Sample source in which we categorized in human & non-human source for the sake of subgroup meta-analysis showed that higher rates of VRE were isolated from non-human as compared to a human source. This may be due to most of the articles included based on our inclusion criteria is from non-human sources as different wild & domestic animal wastes or byproducts, poultry, birds, and environmental sample was compiled for analysis. This part of the study strained the one health approach, which is an important way of combating antibiotics resistance which worsens the world know a day's [57].

Conclusion
Our meta-analysis finding from one health perspective showed that there is a high rate of Vancomycin resistance enterococci circulating in Africa based on the available articles. Availability of data and material: All the data supporting the findings can be obtained from the corresponding author.

Competing of interest:
The authors declare that they have no competing interests     Figure 1 the flow daigram for the article selection of vancomycin resistance entrococcus in Africa with a onehealth approach: a systematic review and meta-analysis 20 Figure 2 shows that the subgroup analysis of VRE at country level 21 Figure 3 shows the subgroup analysis based on the source of the sample for VRE in Africa

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