A Systematic Review of the Outbreak of Elizabethkingia Anophelis

The recent outbreak of Elizabethkingia anopheles in Midwest countries has caused a number of deaths. Notably Elizabethkingia anopheles causes neonatal meningitis, bacteraemia, sepsis, blood stream infections and respiratory infections. This infection may pose serious threats to public health because of lack of sufficient research and its endemic potential unknown. 
This systematic review was meant to develop a deeper insight into the current status of E. anophelis related evidence and to highlight areas that need further research. Reviewing existing literature will help other researchers in identifying and addressing the knowledge gaps. 
Various free access databases such as Google Scholar, Scopus, PubMed, and Science Direct were employed for literature survey. All articles that have been published since 2011, when the outbreak was reported for the first time have been included in this systematic review. The research related to this subject is in earlier stages and little information is currently available. Future studies must focus on the molecular basis, control, prevention, and therapeutics of E. anophelis infection to mitigate its increasing risk. This review is meant to provide baseline data for future research. Scientific community must carry out research on infections caused by E. anophelis mosquito else it will result in a disastrous outbreak.


Introduction
Genus Elizabethkingia is a part of family Flavobacteriaceae and phylum Bacteroidetes.It is a non-motile, ubiquitous, and aerobic bacterium mostly found in the gut of Anopheles mosquito and colonizes the human respiratory tract.Four different species that belong to the genus Elizabethkingia are E. miricola, E. meningoseptica, E. endophytica, and E. anophelis.E. meningoseptica is a nosocomial pathogen that affects patients on hemodialysis [1,2]  Phylogenetic analysis revealed that E. anophelis is different from the closely related species E. miricola and the related group E. meningoseptica (Figure 1).

Quality Assessment
Eligible publications included all research articles or original studies related to E. anophelis from 2011 (when it was initially reported) to 2016.The authors analyzed the available literature independently and removed the duplicates.

Data Synthesis
A total of 13 articles were included and Microsoft Excel spreadsheet was employed to record the relevant information such as the author(s), method, key findings, and conclusion.

Results
A record of primary literature published since E. anophelis was first reported was compiled after a thorough literature search.It included peer-reviewed articles available in the English language.Table 1 depicts the key findings, method, study areas, and study design of all the documents that met the inclusion criteria.

Discussion
In this review, 14 records were identified that included 11 original research articles and 2 case reports published between 2011 and 2016.These studies highlighted the vector potential of mosquitoes for the transmission of E. anophelis to humans.
There is strong evidence that E. anophelis transmits from mother to fetus and this infection is currently circulating in the US states of Michigan, Illinois and Wisconsin.The prevalence of E. anophelis is much higher than E. meningoseptica and E. miricola [25].Previous studies showed that E. anophelis associated bacteremia carries high morbidity and mortality [26].Accumulating evidence suggests that E. anophelis is misidentified as E. meningoseptica but MALDI-TOF MS is the most appropriate choice for the accurate and rapid diagnosis of E. anophelis infection.
The complete genomic sequences of four different strains collected during a recent outbreak of 2015-16 were deposited to GenBank under the BioProject no.PRJNA315668 [26,28].Previously, complete genomic sequences of two strains R26 T and Ag1 isolated from the midgut of the malaria mosquito Anopheles gambiae were available under the GenBank accession numbers ANIW00000000 and AHHG00000000, respectively.Likewise, the genomic sequence of E. anophelis strain EaAs1 isolated from the Asian Department of Life Sciences Volume 3 Issue 1, 2021 malaria mosquito Anopheles stephensi was deposited at GenBank under the accession no.LFKT00000000 [27].
A study demonstrated the molecular basis of Elizabethkingia infections and host mosquito interactions and also introduced the techniques used for the integration of foreign DNA into the chromosome and the expression of the gene of interest in commensal Elizabethkingia [29,35].This study provided future avenues for the development of novel biocontrol agent diseases caused by mosquitoes.The reporter strain, specifically that was GFPbased or NanoLuc-based, allowed the understanding of bacterial infection, in vivo cell localization, and gene regulation [35].
Immunocompromised patients are known to be mostly infected by the genus Elizabethkingia and a number of new species of genus were reported in the last decade.E. anophelis is the most prevalent species of this genus.This genus of pathogen is sensitive to minocycline; however, it is resistant to β-lactam inhibitors, aminoglycosides, β-lactams, and carbapenems.

Conclusion
To conclude, E. anophelis related research is in its initial stages.This review identified the knowledge gap with respect to therapeutics, pathogenesis, transmission, phylogenetics, and molecular biology of the infection.

E
. anophelis is a gram-negative bacteria isolated from the midgut of the anopheline mosquito.Studies involving a three-year long outbreak in Taiwan spanning the time period 2015-2018 resulted in the Department of Life Sciences Volume 3 Issue 1, 2021 identification of a specific E. anophelis strain.Transmission mechanism patterns in 26 patients were studied using Pulsedfield gel electrophoresis (PFGE) and through complete genome sequencing [14].

Figure 1 .
Figure 1.Phylogenetic tree of Elizabethkingia species [13] A study was carried out in Saudi Arabia of 27 patients hospitalized between June 2013 and May 2019 and suspected of having Chryseobacterium / Elizabethkingia spp infection.Blood culture studies showed that Elizabethkingia spp indeed was the most prevalent among the pathogens isolated [15] In another study undertaken in Singapore from 2009 to 2017, 79 blood culture

Figure 2 .
Figure 2. Confirmed cases and deaths during the recent deadly outbreak of E. anophelis in the Midwestern states