Spotlight on the epidemiology and antimicrobial susceptibility profiles of Vibrio species in the MENA region, 2000–2023

Abstract

Recent cholera outbreaks in many countries in the Middle East and North Africa (MENA) region have raised public health concerns and focused attention on the genus Vibrio. However, the epidemiology of Vibrio species in humans, water, and seafood is often anecdotal in this region. In this review, we screened the literature and provided a comprehensive assessment of the distribution and antibiotic resistance properties of Vibrio species in different clinical and environmental samples in the region. This review will contribute to understanding closely the real burden of Vibrio species and the spread of antibiotic-resistant strains in the MENA region. The overall objective is to engage epidemiologists, sanitarians and public health stakeholders to address this problem under the One-health ethos.

Plain Language Summary

The Vibrio genus contains many bacterial species normally found in freshwater, estuaries and marine environments. Some of these species can be transmitted by water and food and can make people severely ill. For instance, some groups of the bacterium Vibrio cholerae (serogroups O1 and O139) can cause serious watery diarrhea called cholera. Other pathogenic Vibrio bacteria can cause other types of infections such as gastroenteritis and wound infections. Some of these bacteria are becoming increasingly resistant to antibiotics, which will threaten and complicate therapy. This review discusses the occurrence and antibiotic resistance of different important Vibrio species in the Middle East and North Africa (MENA) region.

Plain language summary

Article highlights.

Overview of Vibrio species

• Vibrio spp. are Gram-negative, curved rod-shaped bacteria and are part of the normal freshwater, estuarine and marine environment flora.

• Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. alginolyticus are among the most common pathogenic species.

• Vibrio spp. cause two major groups of human diseases: cholera and non-cholera infections.

• Cholera disease is a mild to potentially fatal acute secretory diarrhea caused only by toxigenic serogroups O1 and O139 of V. cholerae after the ingestion of contaminated water or food.

• Non-cholera infections or vibriosis are caused by non-O1/non-O139 V. cholerae or NOVC serogroups, non-toxigenic serogroups O1 and O139 of V. cholerae and non-V. cholerae species such as V. parahaemolyticus. The clinical presentation of vibriosis is diverse and could be diarrhea, wound infections, septicemia and other extra-intestinal infections following the ingestion of raw, undercooked, or mishandled seafood, or exposure of open wounds to contaminated water.

• Vibrio infection is managed differently according to the pathogen, route of infections and symptoms.

Vibrio in the Middle East & North Africa region (MENA region)

Vibrio cholerae serogroups O1 & O139

• Cholera thrives in some MENA countries in epidemic and endemic patterns and many recent outbreaks have been described in some countries after decades of cholera-free status (such as Lebanon).

• Isolates with an extended spectrum of antibiotic resistance have been described, with multi-drug resistant (MDR) plasmids reported in Yemen and Lebanon.

Non-cholera Vibrio cholerae

• Clinical cases of non-toxigenic V. cholerae O1 and NOVC were described and the infection sources of NOVC were usually attributed to seafood and swimming.

• NOVC clinical isolates were more susceptible to antibiotics, with sporadic resistance patterns compared with V. cholerae serogroups O1 and O139.

Vibrio parahaemolyticus, Vibrio vulnificus, & Vibrio alginolyticus

• Similar to NOVC, many reports described the widespread occurrence of V. parahaemolyticus, V. vulnificus and V. alginolyticus in aquatic environments and seafood.

• The clinical data on non-cholera species in terms of morbidity and mortality are scarce, with only a few reports documenting clinical cases and outbreaks of V. parahaemolyticus.

• Despite the notable heterogeneity of results between articles, disturbing antibiotic resistance levels of Vibrio spp. were documented and MDR strains were also described in the MENA countries.

• Species-based differences in antibiotic susceptibility profiles were noted, but more studies are needed to validate these observations.

• In the majority of MENA studies, ciprofloxacin appears to retain its effectiveness, but reports with notable resistance rates have been emerging.

Conclusion & perspectives

• Although the real burden of Vibrio species is underestimated due to weak or incomplete surveillance, sporadic reports from the MENA region highlighted a consequential impact at the clinical level and a concerning level of antibiotic resistance.

• There is a paramount need for systematic surveillance of the occurrence of Vibrio spp. in clinical samples and continuous surveys of MDR Vibrio spp. in aquatic environments and food.

• The adoption of a one-health approach, including a vigilant use of antibiotics in all ecosystems, is required to tackle the emergence and dissemination of resistance.

1. Overview of Vibrio species

Vibrio spp. are Gram-negative, curved rod-shaped bacteria that constitute normal freshwater, estuarine and marine environment flora [1]. Of 152 Vibrio species identified till now [2], 12 could cause severe human infections [3], with the most common pathogenic species being Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. alginolyticus [1]. Two major groups of human diseases caused by these vibrios could be differentiated; cholera and non-cholera infections. Cholera disease is mild to potentially fatal acute secretory diarrhea following the ingestion of contaminated water or food. Only toxigenic serogroups O1 and O139 of V. cholerae, which can produce the cholera toxin, are responsible for cholera disease [4,5], although the majority of infected people are asymptomatic. The burden of cholera disease is substantial with an estimated number of 1.3 to 4.0 million cholera cases per year, and 21,000 to 143,000 deaths worldwide [6]. Non-cholera infections or vibriosis are caused by non-O1/non-O139 V. cholerae or NOVC serogroups, which are V. cholerae serogroups not agglutinated with O1 or O139 antiserum, non-toxigenic serogroups O1 and O139 of V. cholerae, and non-V. cholerae species such as V. parahaemolyticus. The clinical presentation of vibriosis varies based on the species of the pathogen, route of transmission and host susceptibility. It could be diarrhea, wound infections, septicemia and other extra-intestinal infections [1] that occur after the ingestion of raw, undercooked, or mishandled seafood, or exposure of open wounds to contaminated water [7–11].

The management of Vibrio infection also varies according to the pathogen, route of infections and symptoms. While many infections caused by Vibrio spp. are self-limiting and require only supportive care, medical intervention is critical for serious infections [1]. For cholera management, antibiotics can shorten the volume and duration of diarrhea and lessen the excretion of cholera in the feces. Global Task Force on Cholera Control recommends antibiotics for cholera patients with severe dehydration or moderate dehydration with ongoing net fluid losses despite rehydration and for patients with coexisting conditions or comorbidities (including pregnancy), regardless of the degree of dehydration. According to the Global Task Force on Cholera Control, doxycycline is endorsed as a first-line treatment for all patients, including pregnant women and azithromycin or ciprofloxacin as the alternative drugs of choice if resistance to doxycycline was documented [12]. However, tetracycline, doxycycline, fluoroquinolones, co-trimoxazole, erythromycin and azithromycin are the most frequently used antibiotics for treating cholera patients [13]. Notably, doxycycline or quinolone are frequently used for V. parahaemolyticus, while doxycycline and a third-generation cephalosporin are proposed as initial treatment regimens for V. vulnificus [14]. In the USA, quinolones (56.1%) were the most commonly prescribed antibiotics for patients with Vibrio infections, followed by cephalosporins (24.1%), tetracyclines (23.5%) and penicillin (15.4%) [15]. As antibiotic resistance continues to emerge as a global concern, the choice of local antibiotics for the treatment of cholera and vibriosis patients should be guided by frequent antibiotic susceptibility testing on clinical V. cholerae and non-V. cholerae isolates.

Assessing the true burden of Vibrio infections worldwide remains elusive because only a few countries such as the USA have set up systematic surveillance for Vibrio spp. [1]. With regards to the Middle East and North Africa (MENA) region, many countries are grappling with a multitude of crises, including severe economic instability and wars, which are actively weakening and/or obliterating public health systems. The surveillance of Vibrio spp., particularly of non-V. cholerae, outside outbreaks and epidemics does not exist in almost all MENA countries. In addition, the epidemiology of these species within this region, including prevalence and antibiotic resistance, is scattered across articles published with no global perspective. Our aim in this review was to collect relevant information on Vibrio in the MENA countries and present it in one single report to critically assess the epidemiological burden of Vibrio spp. in the MENA region from a One Health perspective. The prevalence of Vibrio spp. and antibiotic resistance were emphasized and discussed. Providing baseline information on antibiotic resistance levels could inform public health authorities and physicians across the MENA countries of appropriate antibiotics that have retained their activity until now.

2. Vibrio in the Middle East & North Africa region (MENA region)

Overall, we described and discussed in this review the occurrence of the most frequent pathogenic Vibrio species and their antibiotic resistance profiles in the MENA countries; starting with V. cholerae serogroups O1 and O139 followed by examining the serogroups of V. cholerae not inducing cholera, V. parahaemolyticus, V. vulnificus and V. alginolyticus. Tables 1–3 in this review and Supplementary Tables S1–S5 in the supplementary material, include data on the prevalence and antibiotic resistance profiles of Vibrio spp. from 104 studies conducted across the MENA region. In order to prepare these tables, the literature was specifically mined for studies tackling either the prevalence of Vibrio species in clinical or environmental settings in the MENA region or the antibiotic resistance profiles of Vibrio isolates from the MENA region. Medline/PubMed was the main searched database, which was filtered by using the terms Vibrio with one of the MENA countries' names (Vibrio AND MENA country name) and restricting the search date from January 1, 2000, to September 9, 2023. The references of the retrieved records were also reviewed for relevant citations. Our inclusion criteria focused on articles written in English or French, stating the prevalence of positive samples for Vibrio spp., displaying the distribution of antibiotic resistance phenotypes with relevant antimicrobial susceptibility testing methods, relying on biochemical or molecular identification methods and representing case reports with available antimicrobial susceptibility data. Articles investigating microbiomes, and articles with experimental and biotechnological purposes were excluded from this study. While the data from reviews and meta-analyses were excluded from the tables and supplementary tables of this review, they were discussed in the text as necessary. When the antimicrobial susceptibility pattern for different Vibrio species or V. cholerae serogroups (O1 and non-O1) was merged, the article was excluded, unless it discussed the prevalence of Vibrio-positive samples. For articles that described data from the MENA region and other countries, only data related to MENA countries were included when possible. Only the percentage of resistant isolates was communicated, and isolates with intermediate resistance were considered susceptible to the antibiotic. Members of the Vibrio genus that were previously classified as species, such as Photobacterium damselae (formerly Vibrio damsela), were removed from the total count of Vibrio spp. in case of misclassification in an article.

Table 1.

Percentage of resistance to different antibiotics in V. cholerae O1 isolated from clinical settings in the MENA region.

Serotype	Country	Study Year	Isolate No	AMPa	TET	NAL	CIP	SXT	ERY	STR	CHL	Ref.
Ogawa	Algeria	2018	20	0%	0%	100%	0%b	100%	ND	100%	0%b	[16]
Ogawa	Djibouti	2000–2001	25	92%	56%	NDc	ND	88%	100%	ND	88%	[17]
Ogawa/Inaba	Iran	ND	121	1%	53%	91%	0%	ND	1%	ND	ND	[18]
Ogawa/Inaba	Iran	2002–2003	74	ND	82.4%	ND	0%	89%	55.4%	ND	31%	[19]
Inaba	Iran	2005	50	42%	84%	ND	0%	86%	4%	88%	86%	[20]
Inaba	Iran	2005	25	52%	80%	ND	0%	92%	ND	92%	88%	[21]
Inaba	Iran	2005	60	ND	23%	ND	8%	98%d	62%	ND	ND	[22]
Inaba	Iran	2005–2007	107	ND	ND	ND	ND	ND	ND	90.7%	99%	[23]
Inaba	Iran	2008	70	100%e	27.9%	100%	ND	95.7%	65.1%	ND	ND	[24]
Ogawa/Inaba	Iran	2008	220	ND	0%	100%	0%	100%	0%	ND	0%b	[25]
ND	Iran	2004–2010	94	0%	0%	ND	0%	97.9%	0%	97.9%	0%	[26]
Ogawa	Iran	2011	239	46%	15.1%	ND	0%	95.4	5.4%	ND	ND	[27]
Ogawa	Iran	2011	61	0%	19.7%	96.7%	0%	91.8%	59%	ND	ND	[28]
Inaba	Iran	2012–2013	20	ND	50%	ND	ND	60%	ND	100%	0%	[29]
Inaba	Iran	2012–2013	30	0%	50%	ND	0%	60%	100%	100%	0%	[30]
Inaba	Iran	2013	60	0%	100%	100%	0%	100%	0%	ND	ND	[31]
Inaba	Iran	2013	33	ND	100%	100%	0%	100%	ND	ND	0%	[32]
Inaba	Iraq	2015	194	0%	0%	100%	ND	ND	0%	ND	0.5%	[33]
Inaba	Kuwait	2015	2	0%	0%	100%	0%	0%	0%	0%	0%	[34]
Ogawa	Yemen	2016–2017	39	0%	0%	100%	0%b	0%	0%	0%	0%	[35]
Ogawa/Inaba	Yemen	2018	623	ND	0%	99.6%	0%	0%	ND	ND	ND	[36]
Ogawa/Inaba	Yemen	2019	2172	100%	0%	100%	0%	100%	ND	ND	ND	[36]

^aAMP for ampicillin, TET for tetracycline, NAL for nalidixic acid, CIP for ciprofloxacin, SXT for co-trimoxazole, ERY for erythromycin, STR for streptomycin, CHL for chloramphenicol.

^bAlthough all isolates are susceptible; they all demonstrated a decreased susceptibility to that antibiotic.

^cND for not determined.

^dSXT was tested on 40 isolates in reference [22].

^eIf the ampicillin was not tested but the amoxicillin was, the resistance percentage toward amoxicillin was mentioned.

Table 2.

Percentage of antibiotic resistance in non-O1 and/or non-O139 V. cholerae isolates from the MENA region.

Country	Setting	Study Year	Isolate No	AMPa	TET	NAL	CIP	SXT	ERY	STR	CHL	Ref.
Iran	Clinical	2008	40	3.2%b	0%	29%	NDc	29%	77.4%	ND	ND	[24]
Iran	Water	ND	25	16%	12%	ND	0%	16%	ND	12%	8%	[21]
Iran	Surface water	2006	37	27%	11%	ND	0%	22%	8%	16%	5.4%	[37]
Iraq	Water from rivers	2009	5	0%	0%	0%	0%	0%	0%	ND	0%	[38]
Morocco	Suburban and rural groundwater supplies	ND	317	42%	2%	0%	ND	ND	18%	62%	0%	[39]
Morocco	Wastewater	2007	21	14.3%b	ND	23.8%	ND	19%	ND	ND	ND	[40]
Morocco	Wastewater	ND	14	14.3%b	ND	0%	0%	0%	ND	ND	ND	[41]

^aAMP for ampicillin, TET for tetracycline, NAL for nalidixic acid, CIP for ciprofloxacin, SXT for co-trimoxazole, ERY for erythromycin, STR for streptomycin, CHL for chloramphenicol.

^bIf the ampicillin was not tested but the amoxicillin was, the percentage toward amoxicillin was mentioned.

^cND for not determined.

Table 3.

Percentage of antibiotic resistance in non-cholera Vibrio species from the MENA region not represented in case reports.

Speciesa	Country	Study Year	Sample type	Isolate No	AMP	TET	NAL	CIP	SXT	ERY	GEN	CHL	Ref.
VP	Lebanon	2017	Stool specimens from humans	7	100%	0%	NDb	0%	ND	ND	0%	0%	[42]
VP	Egypt	ND	Fish	29	34.5%	51.7%	82.7%	37.9%	ND	100%	31%	ND	[43]
VP	Yemen/Jordan	ND	Fish	40	20%	18%	0%	0%	0%	ND	0%	2%	[44]
VP	UAE	2017	Fish and shellfish	15	100%, 27%c	ND	ND	ND	40%, 8%	100%, 62%	ND	ND	[45]
VP	Saudi Arabia	2015–2016	Seawater	40	10%	0%	0%	ND	0%	ND	2.5%	12.5%	[46]
VP	Morocco	ND	Shellfish, seawater and sediments	22	100%	ND	0%	0%	0%	ND	0%	ND	[47]
VP	Morocco	2018–2019	Seawater, bivalves and sediments	20	60%	ND	ND	0%	ND	ND	5%	5%	[48]
VP	Tunisia	2009	Water	5	100%	0%	80%	ND	0%	80%	0%	0%	[49]
VP	Tunisia	2008–2009	Fish	9	100%	88.9%	ND	ND	88.9%	ND	33.3%	77.8%	[50]
VP	Tunisia	2009	Shellfish hatchery	5	80%	0%	0%	0%	0%	40%	0%	0%	[51]
VP	Tunisia	2018	Seawater	9	ND	0%	0%	0%	0%	ND	11%	0%	[52]
VP	Tunisia	ND	Marine fish hatchery	1	100%	ND	100%	ND	ND	ND	100%	100%	[53]
VP	Egypt	2021	Water and dairy products	6	100%	16.7%	0%	0%	ND	83.3%	33.3%	0%	[54]
VA	Egypt	2019	Fish and shellfish	50	96%	28%	42%	14%	18%	58%	2%	ND	[55]
VA	Morocco	2018–2019	Seawater, bivalves and sediment	51	57%	ND	ND	37.3%	ND	ND	6%	0%	[48]
VA	Morocco	ND	Wastewater	10	60%d	ND	0%	0%	0%	ND	0%	ND	[41]
VA	Saudi Arabia	2003–2004	Fish	5	33.3%	66.7%	33.3%	ND	ND	ND	ND	33.3%	[56]
VA	Saudi Arabia	ND	Offshore site (Red Sea)	1	100%	100%	ND	0%	ND	ND	ND	ND	[57]
VA	Tunisia	2003–2005	Fish	34	100%	35.3%	ND	ND	0%	ND	ND	0%	[58]
VA	Tunisia	2009	Water	48	100%	83.3%	70.8%	ND	58.3%	100%	75%	62.5%	[49]
VA	Tunisia	2008–2009	Fish	27	100%	88.9%	ND	ND	51.9%	ND	51.9%	70.4%	[50]
VA	Tunisia	2006	Seawater	28	100%	85.7%	100%	78.6%	64.3%	85.7%	ND	64.3%	[59]
VA	Tunisia	2008–2009	Shellfish	9	100%	100%	ND	22.2%	55.6%	100%	55.6%	77.8%	[60]
VA	Tunisia	2009	Shellfish hatchery	46	100%	49%	10%	10%	39%	85%	80%	55%	[51]
VA	Tunisia	ND	Marine fish hatchery	35	94%	ND	37%	ND	ND	ND	85.5%	48.5%	[53]
VA	Egypt	2010–2011	Fish	7	ND	ND	ND	0%	ND	ND	100%	0%	[61]
VV	UAE	2017	Fish and shellfish	10	100%, 10%c	ND	ND	ND	33%, 2%	100%, 21%	ND	ND	[45]
VV	Qatar	2013–2014	Shellfish	23	74%	0%	ND	ND	ND	45%	ND	ND	[62]
VV	Saudi Arabia	2003–2004	Fish	19	100%	100%	0%	ND	ND	ND	ND	0%	[56]
VV	Saudi Arabia	2010	Seawater	10	100%	0%	ND	ND	0%	ND	90%	ND	[63]
VV	Saudi Arabia	2015–2016	Seawater	52	100%	0%	0%	0%	0%	ND	0%	0%	[64]
VV	Tunisia	2009	Shellfish hatchery	11	100%	18%	0%	0%	0%	18%	0%	0%	[51]

^aVP for Vibrio parahaemolyticus, VA for Vibrio alginolyticus, VV for Vibrio Vulnificus, AMP for ampicillin, TET for tetracycline, NAL for nalidixic acid, CIP for ciprofloxacin, SXT for co-trimoxazole, ERY for erythromycin, GEN for gentamicin, CHL for chloramphenicol.

^bND for not determined.

^cThe first percentage corresponds to the isolates recovered from fish, and the second percentage to isolates from shellfish.

^dIf the ampicillin was not tested but the amoxicillin was, the percentage toward amoxicillin was mentioned.

Of the 104 studies selected based on our inclusion and exclusion criteria, 57 and 61 discussed prevalence or antibiotic resistance, respectively. While 14 articles tackled resistance and prevalence simultaneously. Of the 61 articles discussing the resistance, 13 were case reports presenting resistance of isolates (Supplementary Table S1). The selected studies originated from the following MENA countries; Iran (28 reports), Egypt (19), Tunisia (12), Saudi Arabia (11), Morocco (9), Lebanon (6), Iraq (5), Yemen (3), Kuwait (3), Algeria (2), Oman (2), Djibouti (1), Jordan (1), Qatar (1) and UAE (1). No records were obtained from Bahrain, Libya, Malta, Syria and Palestine using our inclusion criteria.

2.1. Vibrio cholerae serogroups O1 & O139

Cholera is a disease associated with poverty and serves as a key indicator of social development [65]. Unfortunately, cholera thrives in some MENA countries in epidemic and endemic patterns. Cholera has been considered endemic in Iran, Iraq, Djibouti, Syria and Yemen, which are located in the MENA region [66]. Furthermore, in 2022, many countries of the WHO Eastern Mediterranean Region (EMR), which overlaps with some of the MENA countries, experienced cholera outbreaks including Iran, Iraq, Lebanon, Syria and Yemen [67,68].

In Iran, cholera has occurred commonly in the summer and the early months of autumn [25], and occasionally it has been linked to the cross-border movement of humans from Afghanistan and Pakistan [31,69]. Cholera was also detected in Iranian Pilgrims who visited Iraq in 2017 [70]. Iranian outbreaks had generally sporadic forms restricted to small geographic regions within the country, even large ones occurred like that in 2005 and 2011 [20,31,69]. The O1 serogroup was the most prevalent, with serotypes Inaba and Ogawa usually alternating [69]. In the 2005 outbreak, a high percentage of resistance among circulating V. cholerae O1 isolates was noted, including against streptomycin (88%), chloramphenicol (86%), co-trimoxazole (86%), tetracycline (84%) and ampicillin (42%) [20]. Susceptibility to erythromycin differed between provinces and cities; while it was 0% in Tehran, it reached 62% in Hamadan [20,22]. Although papers analyzing isolates from 2005 reported different tetracycline resistance percentages, an overall potential downward trend was observed in subsequent years. However, this trend reversed in 2012 and 2013 when 100% tetracycline resistance was reported (Table 1). Meanwhile, a potential shift in chloramphenicol resistance was also noticed, ranging from 99% in 2005–2007 to 0% in 2013 [23,31,32]. In the 2013 outbreak, the studied isolates were resistant to tetracycline, co-trimoxazole and nalidixic acid but susceptible to erythromycin and ampicillin [31,32]. A systematic review and meta-analysis combining data from 27 Iranian papers, published before July 2018, showed a high resistance rate against numerous antibiotics, including co-trimoxazole (86%), streptomycin (93.8%), nalidixic acid (88.9%), polymyxin (80.7%), furazolidone (69.8%), oxytetracycline (40.2%), tetracycline (34.5%), chloramphenicol (33.6%), ampicillin (32.1%), amoxicillin (30.5%) and kanamycin (29%) [71]. The observed resistance was often associated with the mobile SXT genetic element, a V. cholerae-derived integrating conjugative element (ICE), which was usually detected in more than 95% of the isolates [23,26,29,72], explaining the reported resistance to co-trimoxazole, streptomycin and chloramphenicol. While some studies did not analyze tetracycline resistance determinants [29], tetB, which encodes a tetracycline efflux protein [73], was reported in one study [32].

In Iraq, cholera outbreaks occur every 3 to 5 years [74] as a consequence of a series of wars and damaged urban infrastructure. According to studies, the prevalence of confirmed cholera among cholera-suspected cases varies according to year and province (Supplementary Table S2). The last outbreak was declared on June 19, 2022, with a total of 3,063 confirmed cholera cases and 19 deaths across the country as reported on November 02, 2022 [75], with cases still reported in 2023 [76]. Despite records mentioning a high percentage of tetracycline resistance in the 2001 outbreak [77], reports from 2007–2009 and 2015 demonstrated a narrower resistance profile with susceptibility to tetracycline [33,38]. Approximately, 97.5% of the isolates from 2007–2009 were resistant to co-trimoxazole, nalidixic acid and chloramphenicol, but susceptible to tetracycline, erythromycin, ampicillin and ciprofloxacin. However, a small percentage of the V. cholerae analyzed were non-O1 isolates [38]. Similarly, isolates from the 2015 outbreak were 100% resistant to nalidixic acid but were fully or moderately susceptible to erythromycin, tetracycline and chloramphenicol [33]. V. cholerae O1 isolates imported from Iraq to Kuwait also exhibited the aforementioned susceptibility pattern [34].

Yemen, a war-torn (2014-present) country, has faced one of the most severe cholera epidemics in recent history; with over 2.5 million cases and 4,000 deaths since September 2016 (statistics as reported in April 2021) [78]. Genomic analysis traced the V. cholerae O1 El Tor serotype Ogawa isolates in 2016–2017 to sublineage AFR13 (formally known as T13) that originated in South Asia and has been circulating in Eastern Africa since 2015, before appearing in Yemen in 2016 [35]. Isolates from Yemen exhibited resistance to nalidixic acid, nitrofurantoin and the vibriostatic agent O/129, with a decreased susceptibility to ciprofloxacin. A ∼10 kb deletion in the chromosomal mobile genetic element SXT/R391 ICE (called ICEVchInd5/ICEVchBan5) explains this narrow antibiotic resistance phenotype leading to the loss of four genes that encode resistance to sulfonamides (sul2), chloramphenicol (floR) and streptomycin (strA and strB). However, the fifth gene in this region, which encodes resistance to the vibriostatic agent O/129 (dfrA1), remained in the Yemeni isolates [35]. The resistance to nalidixic acid and the decreased susceptibility to ciprofloxacin are explained by mutations in the DNA gyrase gene, gyrA and the topoisomerase IV gene, parC, which result in the S83I and S85L amino acid substitutions, respectively [35]. Resistance to nitrofurans is explained by the mutations in the VC_0715 and VC_A0637 genes, which encode orthologs of NfsA and NfsB proteins of E. coli K12, leading to the R169C amino-acid substitution and a premature stop codon (Q5Stop), respectively.

Resistance to polymyxins has been used as a marker of the El Tor biotype since the start of the seventh cholera pandemic in 1961. The latter is in contrast to the classical biotype, which is susceptible to polymyxin B and responsible for the six previous pandemics. Notably, the restored susceptibility to polymyxin B in the Yemeni El Tor isolates, which was first reported in Kolkata India in 2012 [79], is attributed to a mutation in the vprA gene, resulting in the amino acid D89N substitution in VprA (also known as CarR) [35,80]. VprA is essential for the expression of the almFEG operon that is involved in the glycine modification of lipid A [35,81,82]. Alarmingly, epidemiological surveillance in late 2018 showed that V. cholerae in Yemen had turned multidrug-resistant (MDR), exhibiting resistance to multiple drugs including co-trimoxazole, third-generation cephalosporins, macrolides (including azithromycin), suggesting a possible shift in circulating genotypes or acquisition of mobile genetic elements by the original circulating strains [36]. Phylogenomic analysis confirmed the second hypothesis because the original AFR13 Yemeni strain has acquired an IncC-type plasmid named pCNRVC190243, which carried genes encoding an extended-spectrum beta-lactamase (ESBL; bla_PER-7), resistance to sulfonamide (sul1), aminoglycoside (aadA2) and macrolide (mph(A), mph(E) and msr(E)) and a quaternary ammonium compound efflux pump (qac). Plasmid acquisition might be favored by the selection pressure associated with the overuse of macrolides in Yemen to treat severe cholera [36].

In 2022, a cholera outbreak started first in Syria and spread to Lebanon [68]. Nearly 13 years after the last reported cholera outbreak in 2009, Syria announced a new cholera outbreak on September 10, 2022. The outbreak quickly spread across the Syrian governorates leading to 132,782 suspected cases and 104 associated deaths, reported between 25 August 2022, and 20 May 2023, from all 14 Syrian governorates [83].

Nearly three decades after the last outbreak in 1993 [84], Lebanon was considered free of cholera. However, Lebanon notified the WHO of the first new cholera cases on October 6, 2022. The index case was reported to be a Syrian man living in North Lebanon. While the outbreak was contained on January 5, 2023, it resulted in 5,912 suspected cases, with 671 confirmed cases and 23 deaths in the 3 months after notification [85]. A recent study revealed that the 2022–2023 outbreak in Lebanon was fueled by two different strains. One strain of dominant occurrence had a narrower antimicrobial resistance profile (resistance to nitrofurantoin, O/129 and nalidixic acid only, and a decreased susceptibility to ciprofloxacin) due to the 10 kb-deletion in the chromosomal ICEVchInd5 and was related to South Asian isolates. The other strain had a low prevalence with an extended antimicrobial resistance profile (resistance to third-generation cephalosporins, macrolides, sulfonamides, O/129, co-trimoxazole, nitrofurantoin and nalidixic acid, and a decreased susceptibility to ciprofloxacin) due to the presence of a resistance plasmid (pCNRVC190243) and was similar to the Yemeni AFR13 V. cholerae strain [86]. Notably, a study conducted between 2020 and 2021 in Lebanon reported V. cholerae in 0.6% of stool samples from outpatients with acute diarrhea before the cholera outbreak [87]. However, the detection of these cases relied on PCR analysis of the gyrB and toxR genes, which allowed the identification of the Vibrio genus and V. cholerae, respectively but not the serotyping of V. cholerae.

Occasional cholera cases were also notified from other Middle Eastern countries like Kuwait, Qatar, Oman and Saudi Arabia, but these were usually considered imported from other endemic regions and not involved in larger outbreaks [88–90].

In North Africa, Algeria faced a cholera outbreak in 2018, after a lull of more than 20 years, that resulted in 291 suspected cholera cases of which 97 (33.3%) were confirmed as V. cholerae O1 El Tor serotype Ogawa [16]. A meticulous genomic analysis showed that the isolates belonged to a newly introduced strain (sublineage AFR14) into Africa from South Asia rather than the introduction of African sublineages circulating elsewhere in Africa or the re-emergence of any sublineage previously reported in Alegria [16]. All V. cholerae O1 isolates were resistant to streptomycin, co-trimoxazole, and nalidixic acid and had a decreased susceptibility to ciprofloxacin but were susceptible to doxycycline, azithromycin, β-lactams and colistin [16]. The Algerian isolates shared with Yemeni isolates the same mutation signatures in gyrA, parC, nfsA, nfsB and vprA, but they had a complete ICEVchInd5 with all five-member genes (strAB, floR, sul2, dfrA1); explaining the wider resistance.

Although Djibouti is deemed a cholera-endemic area, antibiotic susceptibility data are scarce. Djibouti experienced an epidemic in 2000, which was imported from Somalia and lasted 33 weeks, with 1930 patients hospitalized [17]. O1 El Tor serotype Ogawa was the main serotype isolated during this epidemic and was characterized by a multidrug-resistance pattern, specifically to ampicillin (92%), co-trimoxazole (88%), tetracyclines (56%) and erythromycin (100%). The appearance of MDR V. cholerae strains was considered a turning point in the history of cholera in Djibouti, where more susceptible strains used to circulate. For instance, a strain from 1993 was susceptible to ampicillin, tetracycline and sulfonamides [17].

Although a relatively limited number of studies are presented in Table 1, with the majority originating from Iran, they highlighted the extent to which V. cholerae is evolving and becoming resistant, even, in instances, exhibiting MDR phenotype with resistance percentages up to 100% for tetracycline, nalidixic acid and co-trimoxazole [31]. A recent meta-analysis study addressed the antibiotic resistance of V. cholerae. Rostami et al. demonstrated geographical differences in resistance patterns of clinical V. cholerae isolates, with increasing resistance trends to furazolidone (76%), nalidixic acid (55%) and nitrofurantoin (65%). According to Rostami et al., novobiocin and ofloxacin are the most effective in Africa, ciprofloxacin in North America and gatifloxacin and levofloxacin in Asia [91]. Additionally, another meta-analysis study revealed considerable weighted pooled resistance rates in clinical V. cholerae O1/O139 isolates against co-trimoxazole (79%), erythromycin (36%) and tetracycline (20%), but low resistance against azithromycin (1%), ciprofloxacin (3%) and doxycycline (7%). Notably, resistance to co-trimoxazole, ciprofloxacin and tetracycline has been rising during the 1980–2020 years [92]. Similarly, a higher resistance percentage to tetracycline (50%) and doxycycline (28%) for serogroup O1 has been estimated in the meta-analysis study of Ahmadi et al. [93].

Few studies on V. cholerae in the MENA region tackled resistance to ß-lactams and usually communicated susceptibility to the tested cephalosporins (Supplementary Table S3). Among the ß-lactams, resistance to ampicillin was the most examined antibiotic, with resistance ranging from 0 to 100% (Supplementary Table S3). In the meta-analysis study of Nateghizad et al. that investigated resistance of V. cholerae to antibiotics that inhibit cell wall synthesis, cefepime, imipenem and aztreonam were the most efficient antibiotics, against which the isolates were fully susceptible. Additionally, carbenicillin (95%) and polymyxin B (77%) had the maximum resistance rates. Second-generation cephalosporins had higher resistance rates [cefamandole (50%), cefoxitin (56%) and cefuroxime (9%)] compared with first [cefalexin (8%) and cephalothin (7%] and third generation [Cefixime (37%), cefotaxime (15%), ceftazidime (5%) and ceftriaxone (9%)] [94]. However, these observations in the MENA require, in several instances, more in-depth studies that focus on a larger number of isolates with better antibiotic resistance analyses that account for both phenotype and underlying genetic determinants.

2.2. Non-cholera Vibrio cholerae

Non-cholera V. cholerae encompasses the non-toxigenic V. cholerae O1 and O139 and NOVC; and have been associated with over 100 cases annually in the USA, making them the third most commonly reported group of Vibrio bacteria [95]. According to estimates, NOVC accounts for 1% and 3.4% of acute diarrhea cases in developing and developed countries [96] and is considered an emerging potential pathogen of clinical relevance [97]. A 31-year surveillance (1984 -2014) identified 52 vibriosis cases caused by toxigenic NOVC (serogroups O75 and O141) in the USA [98].

About 3% of patients, referred to health centers in the city of Qom, Iran, with gastrointestinal symptoms were found to be infected with NOVC [99]. However, assessing the true clinical burden of NOVC is challenging in the MENA region because of the absence of systematic screening and typing of V. cholerae isolates. Regardless, the burden must not be neglected, with many cases in the MENA countries associated with invasive septicemia and tissue infections, usually happening in patients with underlying conditions (Supplementary Table S1). Seafood and swimming were associated with infections among case reports with known sources. In the MENA, the prevalence of positive NOVC samples reached 15.4% in shellfish in Morocco [100], while higher percentages of untyped V. cholerae were recorded in Egypt, including 31.3% among moribund and freshly dead fish (Nile tilapia) and 45% among fish and shellfish which mostly were apparently healthy [101,102]. These percentages are notably above the global pooled prevalence of V. cholerae in fishes, which is 9.56% [103]. With regards to water, approximately 30.4% of surface water samples used for agriculture in the Qom province in Iran were positive for NOVC (65). A similar percentage (36.5%) was detected in environmental water samples from the Dhahira region in Oman [104]. Although not typed, V. cholerae was detected in illegitimate drinking water (not under governmental inspection and control) in the Giza governorate, Egypt and in patients with diarrhea and gastroenteritis [105]. Seawater samples from Tunisia were negative for V. cholerae [52,106], further stressing the non-halophilic nature of V. cholerae, which is usually considered more prevalent in freshwater than seawater [107]. In contrast to the North Sea, NOVC and V. vulnificus prevailed in the Baltic Sea, while V. alginolyticus and V. parahaemolyticus were less common, probably due to lower salinities [8].

Non-toxigenic V. cholerae isolates are associated with diarrheal disease throughout the world. Recently, genomic epidemiology has uncovered two epidemic non-toxigenic lineages spreading worldwide over the past 100 years [108]. Old reports from Saudi Arabia identified a recurrent summer pattern of non-toxigenic V. cholerae O1 Ogawa infections during surveillance of V. cholerae in the Eastern Region of Saudi Arabia from 1996 to 1997, which was attributed to a local environmental reservoir [109]. A case report has also described an unusual case of bacteremia and primary peritonitis in a patient with liver cirrhosis caused by V. cholerae O1 serotype Ogawa, but the mode of infection remained unclear (Supplementary Table S1) [110]. In Yemen, 16% of 260 V. cholerae isolates sampled during the Yemeni outbreak between 2018 and 2019 were non-toxigenic from divergent non-seventh pandemic El Tor (7PET) lineages, likely reflecting occasional gut colonization by endemic strains [36]. Out of 26 cases of cholera with almost mild symptoms in Oman, 12 were caused by V. cholerae O1, El Tor and 14 by non-O1, and were geographically restricted in one district of the Dhahira region. This atypical presentation of V. cholerae might be due in part to the endemicity of non-toxigenic O1 in some parts of Oman [104].

With regards to antibiotic resistance, the susceptibility patterns of clinical NOVC isolates from Iranian patients with acute gastroenteritis referred to the city of Karaj (west of Tehran) and nearby areas during the 2008 outbreak differed from the O1 Inaba isolates; with no considerable resistance found except for erythromycin (Table 2) [24]. Usually, the isolates from case reports were susceptible to antibiotics with sporadic resistance patterns identified in Lebanon and Saudi Arabia, though not every tested antibiotic is mentioned (Supplementary Table S1). A meta-analysis carried out on clinical NOVC showed resistance rates below those of O1 and O139 serogroups [92,111], including resistance to erythromycin (10% vs 36%), co-trimoxazole (27% vs 79%), tetracycline (13% vs 20%), but higher resistance against ciprofloxacin (5% vs 3%) [92,111]. The highest resistance rates were found against ampicillin (51%), streptomycin (40%), co-trimoxazole (27%), neomycin (27%), nalidixic acid (20%), while the lowest were against gentamicin (1%), kanamycin (2%), ciprofloxacin (5%) and chloramphenicol (5%) [111]. An increasing trend in resistance to ciprofloxacin, nalidixic acid, gentamicin and norfloxacin among clinical NOVC was observed from 2000 to 2020, which was in contrast to the decreased resistance to erythromycin, tetracycline, chloramphenicol, co-trimoxazole, ampicillin, streptomycin, kanamycin and neomycin during the same period [111]. Interestingly, the genome analysis of seven isolates from adult patients with cholera-like symptoms in Qatar identified several antibiotic resistance genes in V. cholerae O1 El Tor (sul2, tet(34), tet(59), dfrA1, aph(3″)-Ib and aph(6)-Id) compared with only tet(34) in NOVC [112].

Like the clinical NOVC isolates, environmental NOVC isolates recovered from surface waters in Iran were significantly less resistant than clinical V. cholerae O1 isolates of serotype Inaba from the 2005 outbreak, with resistance not exceeding 20% against several antibiotics, including co-trimoxazole, tetracycline and streptomycin; however, resistance to polymyxin B (44%) was an exception [21]. Comparable findings were also observed in Iraq [38].

The antibiotic resistance rates of NOVC collected from various sources of water in six studies conducted in the MENA region were relatively low; ranging from 0 to 42% against ampicillin, 0 to 60% against cephalothin, 0 to 12% against tetracycline, 0 to 22% against co-trimoxazole, 0 to 18% against erythromycin and 12 to 62% against streptomycin (Table 2 & Supplementary Table S4) [21,37–41]. In comparison, the majority (67%) of NOVC isolated from clinical, environmental and seafood samples in Germany were susceptible to all antimicrobial agents tested with non-significant elevated percentages in clinical isolates compared with environmental isolates. A notable percentage of strains demonstrated resistance to ampicillin (11%), streptomycin (2%) and sporadically to carbapenems [113]. Another study showed that NOVC isolated from seven recreational bathing areas at German costs from 2017 to 2018 had only resistance to the co-trimoxazole and ß-lactam antibiotics (specifically cefazolin, oxacillin and penicillin) [114].

2.3. Vibrio parahaemolyticus

V. parahaemolyticus has been considered the leading causal agent of gastroenteritis following the consumption of seafood in the USA and in several other parts of the world [95,115]. For example, V. parahaemolyticus was responsible for 20–30% of all food poisoning cases in Japan [115]. In addition to sporadic cases, some strains of V. parahaemolyticus, particularly those belonging to two serotypes O4:K12 and O3:K6, have undergone transcontinental expansion and are involved in recent outbreaks [116,117]. In the MENA region, only a few studies investigated the burden of V. parahaemolyticus. A first-proven V. parahaemolyticus outbreak in the Middle East occurred in Lebanon in 2017 and was caused by an ST3 O3:K6 pandemic clone, which affected patients recalling eating seafood, highlighting the potential burden of this species and the spread of emerging clones in Lebanon [42]. Approximately, 3% of diarrheic patients attending the outpatient clinic at a hospital in Egypt were positive for V. parahaemolyticus but negative for V. cholerae [118]. In fish, the prevalence of V. parahaemolyticus varied according to country and ranged from 0 to 73%, specifically 0% in Algeria and Morocco, 0 to 73% in Egypt, 36.4% in Yemen, 12.4% in Tunisia, 7.5% in UAE, 49% in Jordan and 0 to 7.6% in Saudi Arabia (Supplementary Table S2). Some of these percentages were relatively higher than the global pooled prevalence (24.8%) of V. parahaemolyticus in fish as well as that calculated in Africa (11%), Asia (28%), Europe (6.45%) and North America (34.94%) [103]. The high percentages, like those reported in an Egyptian study (73%), might be due to the health status of sampled fish (diseased or healthy) and the role of V. parahaemolyticus as a causative pathogen of bacterial disease in fish [119]. In shellfish, the prevalence ranged from 0.5 to 19% based on the country, specifically 7 to 16.7% in Egypt, 0.5 to 17.1% in Iran, 4.2 to 8.4% in Morocco, 9.6% in Tunisia, 13% in UAE and 19% in Saudi Arabia (Supplementary Table S2). A preliminary comparison in the case of Egypt could infer elevated percentages of Vibrio in fish compared with shellfish, but this comparison is hindered by heterogeneities in study methodologies and conditions. However, shellfish are notorious for their ability to accumulate and concentrate pathogens, including Vibrio, present in waters to the degree where the number of V. parahaemolyticus and V. vulnificus in shellfish could reach up to 100-fold of that in the surrounding waters [117], which could explain the higher incidences of these species in shellfish compared with fish [120,121]. Also, differences according to the type of sampled shellfish have been reported. While shrimp samples had the maximum prevalence of V. parahaemolyticus (86.7%), exceeding that of fish (53.33%), squid had the same prevalence as in fish, while oysters (40%) had a lower prevalence [122].

In aquatic environments, V. parahaemolyticus is a prominent organism in marine systems, including both near-shore and open ocean environments [123], with optimal salinity for V. parahaemolyticus being in the range of 10‰ to 34‰ [114]. V. parahaemolyticus was recovered from most of the investigated seawater samples in the MENA region (Supplementary Table S2). Similarly, V. parahaemolyticus was the dominant Vibrio species found in North Sea samples, where it was detected in half of the samples between April and November; indicating its potential adaptation to the high salinity of the North Sea [114]. A study examining water resources in Eastern Cape Province, South Africa demonstrated a very low prevalence of V. parahaemolyticus and V. alginolyticus (2% and 3%, respectively) in freshwater samples versus high percentages in brackish water samples (about 51% and 46%, respectively) [124]. Across water bodies in Africa, V. parahaemolyticus was the second Vibrio organism (10.4%) identified after V. cholerae (59.5%), followed by V. alginolyticus (9.8%), V. vulnificus (8.5%) and V. fluvialis (6.6%) [3]. A low number of sediment samples was analyzed in the MENA region; with prevalence reaching up to 40% in Jordan [125]. Sediments are regarded as an important habitat for Vibrio species, with concentrations up to three logs higher than in water samples [114].

A total of 13 publications evaluated the antimicrobial susceptibility profiles of V. parahaemolyticus in the MENA region (Table 3); however, only one article from Lebanon had isolates with clinical origins. The other publications studied isolates from aquatic environments and seafood, except for one that also included additional isolates from dairy products (Table 3). V. parahaemolyticus is commonly regarded as highly susceptible to all antimicrobials, except penicillin [126]. The intrinsic resistance to penicillin is explained by the carriage of bla_{(CARB-17)-like} genes that encode class A carbenicillin-hydrolysing β-lactamase (CARB), conferring resistance to ampicillin, penicillin G, carbenicillin and piperacillin [126]. However, intrinsic resistance toward ampicillin was disproved, because not every V. parahaemolyticus isolate that is a bla_CARB-17 carrier was phenotypically resistant to ampicillin [127]. Of 12 articles testing ampicillin, 9 shared a high level of resistance from 60 to 100%, while the other three had resistance values from 10 to 34.5% (Table 3); corroborating worldwide findings [128]. The clinical isolates in the aforementioned outbreak that happened in Lebanon in 2017 were resistant to ampicillin (100%), ceftazidime (86%), ticarcillin (14%) and amikacin (14%), but susceptible to carbapenem, aminoglycoside (gentamicin, tobramycin), chloramphenicol, quinolone and tetracycline [42]. Notably, these isolates carried bla_CARB-22, explaining resistance to ampicillin, but no other resistance genes were detected [42]. In studies testing susceptibility against cephalosporins, a high percentage of isolates revealed general resistance to cephalothin (above 50%), whenever tested, except for one study that reported 0% resistance to cephalothin, but all the isolates had intermediate resistance to this antibiotic (Supplementary Table S5) [47]. For cefotaxime, only 3 out of 8 studies indicated resistance percentages above 60% to 100%, while the other five studies reported isolates with no or low resistance (up to 5%). While resistance to ceftazidime varied between 0 and 86% across studies, no resistance was reported against carbapenem (Supplementary Table S5).

Regarding the recommended antibiotics for V. parahaemolyticus, ciprofloxacin had a higher efficacy than tetracycline; with 0% resistance rates in almost all reports (Table 3); except one which reported an alarming resistance percentage of about 38% among isolates from fish in Egypt [43]. This high susceptibility toward ciprofloxacin in the MENA region is generally in line with worldwide reports, except for ones describing increased resistance percentages to ciprofloxacin [129]. Although five of nine studies documented no resistance toward tetracycline, the remaining studies reported resistance from 16.7% to 88.9% among V. parahaemolyticus that were mostly isolated from fish in Egypt, Tunisia and Yemen (Table 3). This resistance may be attributed to the use of tetracycline in fisheries to treat infections caused by Vibrio spp. [50,130]. At a global scale, the antibiotic resistance profile to ampicillin, penicillin and tetracycline was considered the most predominant; regardless of the country [128].

V. parahaemolyticus isolates in the MENA region developed high resistance rates against erythromycin (40 to 100%) (Table 3), being generally at the higher end of worldwide reported levels. For instance, in Korea, despite erythromycin being a representative macrolide in fisheries, resistance was as low as 3.3% [130]. Likewise, in China, no resistance was observed [131]. Nonetheless, more than half of the isolates (54.2%) from cultivated oysters and estuarine water in Thailand were resistant to erythromycin [132] in agreement with an Indian study [133], and all the strains involved in an outbreak associated with raw oyster consumption in Spain were erythromycin-resistant [134]. These data from the MENA region require vigilance to erythromycin, a widely used antibiotic in human and veterinary medicine [132]. According to an environmental study, the distribution of erythromycin resistance in the environment is common globally; with its highest prevalence observed in Asia [135], mainly influenced by anthropogenic activities [132].

The majority of isolates in the MENA studies were highly susceptible to co-trimoxazole; except for those recovered from fish and shellfish samples in two studies from UAE and Tunisia, which showed up to 89% resistance [45,50]. The susceptibility toward co-trimoxazole was in marked contrast with the resistance profiles of the isolates from German coasts that demonstrated resistance only to ß-lactam and co-trimoxazole [114], but was in harmony with findings from the Maryland Coastal Bays in the USA [136], and in gastroenteritis patients in Indonesia [137]. Like co-trimoxazole, the majority of MENA studies exhibited susceptibility to chloramphenicol except for two reports from Tunisia; with resistance rates above 77% (Table 3) [50,53], while susceptibility was also revealed elsewhere [128,136].

Among tested aminoglycosides, the V. parahaemolyticus isolates in the majority of the MENA studies showed high resistance rates against streptomycin and kanamycin, but moderate resistance against gentamicin and amikacin with some exceptions (Table 3 & Supplementary Table S5). Resistance to streptomycin has also been acknowledged in many reports [138–140] outside the MENA countries, where 46.2% of the isolates from seafood available on the Polish market that originated from different countries were resistant to ampicillin and streptomycin [141]. This resistance was tied to the potential overuse of these antimicrobials in different applications (treatment, agriculture and aquaculture) during the last decades [141]. The low resistance to gentamicin (10.5%) compared with streptomycin (73.7%) and kanamycin (55.3%) was also seen in Korean isolates from shellfish [139].

2.4. Vibrio vulnificus

In the USA, while V. parahaemolyticus was responsible for most of the vibriosis-confirmed cases, V. vulnificus was liable for most deaths among vibriosis-confirmed cases [95]. Additionally, about 95% of seafood-related deaths were attributed to V. vulnificus [14]. In the MENA region, clinical data are unavailable. In seafood, the percentage of V. vulnificus reached 7.7% in fish and 5.3% in shellfish (Supplementary Table S2) [142,143]. These prevalence values were similar to the global pooled prevalence of V. vulnificus in fish (5.29%) [103]. V. vulnificus was generally not reported in most types of water in the MENA region (Supplementary Table S2). However, while reported as absent in the Tunisian seawater [52], nearly 18% of seawater samples from coastal areas of the Eastern Province of Saudi Arabia were positive for V. vulnificus [64]. These differences can be due to salinity where the optimal salinity for this bacterium ranges from 5‰ to 25‰ [114]. Other studies in the MENA region are needed to gauge an accurate prevalence.

Regarding antibiotic resistance, although studies reported resistance to ampicillin ranging from 10 to 100%, the majority of isolates expressed a high level of resistance, which concurred with other observations [128]. For other ß-lactams, a study on seawater samples collected from the coastal areas of the Eastern Province of Saudi Arabia reported a high level of resistance against cephalothin (73%), moderate resistance against cefoxitin (15%) and no resistance against third and fourth generation cephalosporins and carbapenem [64]. However, accurate levels of ß-lactam resistance could not be derived due to the scarcity of studies. V. vulnificus from the Maryland coastal bays in the USA showed the highest resistance toward cephalothin (42%) and cefoxitin (42%) followed by ceftazidime (36%) [136]. Resistance was also recorded for aminoglycosides; reaching up to 44% for streptomycin, 90% for gentamicin and 70% for amikacin [63,64] (Table 3 & Supplementary Table S5). In comparison, V. vulnificus from clinical and environmental origins in Germany exhibited exclusive non-susceptibility to aminoglycosides [113]. However, in addition to aminoglycosides, resistance of V. vulnificus was also seen toward ß-lactam (specifically penicillin, cefaclor, cefoxitin and cephalothin) in Saudi Arabia [63,64] and to erythromycin and tetracycline in Tunisia [51]. Three of 5 articles revealed a full susceptibility of V. vulnificus toward tetracycline (Table 3), the other two reported 18% and 100% resistance in Tunisian shellfish hatchery and Saudi Arabian fish [51,56]. Percentages of resistance ranged from 18 to 100% toward erythromycin and from 0 to 33% toward co-trimoxazole (Table 3). Fortunately, all tested isolates revealed full susceptibility toward nalidixic acid and ciprofloxacin, as shown elsewhere [113,128,136]. When comparing antibiotic resistance between Vibrio spp., we observed lower resistance rates to tetracycline, nalidixic acid, co-trimoxazole and chloramphenicol in V. vulnificus (Table 3). V. vulnificus isolates from the Louisiana Gulf and Retail Raw Oysters exhibited lower MICs for cefotaxime, ciprofloxacin and tetracycline compared with V. parahaemolyticus [144]. In comparison, alarming resistance levels against carbapenems (70.3% for imipenem), aminoglycosides (67.8% for kanamycin), quinolones (10.8% for ciprofloxacin), macrolide (100% for azithromycin) and chloramphenicol (100%) were seen among V. vulnificus isolated from rustic environment freshwaters in South Africa [145].

2.5. Vibrio alginolyticus

V. alginolyticus is frequently encountered in the marine environment [1]. It was prevalent in water (79%) and sediment (94%) samples from the North Sea of high salinity and in sediments of the intertidal mudflats (Lower Saxony), but had a lower prevalence in Baltic Sea samples with low salinity [8]. V. alginolyticus was the third pathogenic Vibrio species detected across water bodies in Africa; with a percentage of 9.8% [3]. In the MENA region, studies reporting the prevalence of V. alginolyticus in water are scarce and inconsistent; with percentages ranging from 0% to 100% in Tunisian seawater [52,106]. Unlike other Vibrio spp., water is considered the predominant source of infection of V. alginolyticus compared with seafood and the pathogen tends to cause ear and soft tissue infections that rarely progress to septicemia and necrotizing fasciitis, particularly in individuals with weakened immune systems [1,146]. The incidence of V. alginolyticus has increased in the last years to become the second most common species in patients with vibriosis in the USA [95,146]. However, assessment of the clinical impact in terms of morbidity and mortality of V. alginolyticus is unavailable in the MENA region. In seafood in the MENA region, the prevalence is in the range of 0–83.3% in fish and 0.5 to 90.4% in shellfish (Supplementary Table S2), usually exceeding the prevalence of V. parahaemolyticus in studies reporting on both V. parahaemolyticus and V. alginolyticus worldwide [147], which confirms the ubiquity of this species in coastal flora. Ten of 16 papers reported V. alginolyticus in diseased fish with clinical symptoms, indicating potentially its pathogenic role in these fish (Supplementary Table S2). Indeed, V. alginolyticus is one of the known species involved in bacterial infection in fish and aquaculture, where it has been associated with significant economic losses [148–150].

The levels of resistance to penicillins, including ampicillin, ticarcillin and carbenicillin were high, with percentages exceeding 90% against ampicillin in the majority of studies (9 of 11 studies) (Table 3). While resistance to third-generation cephalosporins and carbapenems is generally low, resistance rates of up to 89.3% have been reported for cefotaxime and carbapenems in Tunisia [59], suggesting the potential production of carbapenemase in the isolates as seen elsewhere [151]. Compared with V. parahaemolyticus, remarkably higher levels of resistance were found in V. alginolyticus against tetracycline (28–100%) and ciprofloxacin (0–78.6%) (Table 3 & Supplementary Table S5). Additionally, high multidrug resistance; exhibiting strong resistance to ampicillin, erythromycin, carbenicillin, streptomycin, kanamycin and tetracycline was noted in V. alginolyticus isolates from Monastir lagoon water in Tunisia in comparison to other species [49]. More studies are needed to verify these species-based differences, especially in light of some contradictory findings elsewhere [152]. Similar to other Vibrio spp., a significant degree of resistance was detected against co-trimoxazole (0–64.3%), erythromycin (58–100%), streptomycin (0–100%), gentamicin (0–100%) and chloramphenicol (0–77.8%) (Table 3 & Supplementary Table S5).

3. Conclusion

As discussed above, Vibrio spp. not causing cholera are widespread in the environment and seafood in the MENA countries, and this appeared to be consequential at the clinical level. Concurrently, V. cholerae thrives in some MENA countries in endemic and epidemic scenarios. In 2022, the global number of cholera cases and associated deaths has increased after years of decline, and many MENA countries declared cholera outbreaks (such as Syria and Lebanon) after decades of cholera-free periods [153]. Many factors are associated with the resurgence of cholera in the region; including long-lasting conflicts (such as wars), political turmoil, collapsed economies and natural disasters [67]. Other drivers promoting the spread of Vibrio species include climate change and the increasing consumption of seafood products, particularly those that are raw or undercooked [154]. Similar to findings in other regions [114], the incidence of Vibrio species in the MENA region is driven up by increased water temperature during summer, which could heighten the risk of infections during the summer period [155,156]. However, the incomplete or weak surveillance of Vibrio infections and limited laboratory abilities might impact reporting, preventing the determination of real trends, although some evidence of an upsurge of V. parahaemolyticus infections during the summer was recorded in Lebanon [42]. The heterogeneities of the reported prevalence rates of Vibrio spp. within the same countries or different countries in the MENA region could be caused by many variables, including differences in geographical origin, weather, water salinity conditions, sample type, microbiological methods used for isolation and identification and storage and transportation conditions.

Concerning antibiotic resistance levels of Vibrio spp. were documented and MDR strains were described in the MENA countries [24,46,55]. Among non-V. cholerae, resistance to ampicillin was high across studies (Table 3). Despite the differing rates reported by the studies, high resistance percentages could be noted to other antibiotics, especially tetracycline, co-trimoxazole and erythromycin. Intriguingly, antibiotic resistance patterns also varied according to Vibrio species, but these conclusions need larger and deeper studies to be confirmed. Regardless, the misuse of antibiotics in different fields, including fisheries and aquaculture, agriculture and human and veterinary medicines, has exacerbated resistance rates. For example, out of the 15 largest aquaculture-producing countries, 11 used 67 antibiotic compounds for treatment between 2008 and 2018. Among these 11 countries, about 73% used oxytetracycline, sulphadiazine and florfenicol, while 55% applied sulphadimethoxine, erythromycin, amoxicillin and enrofloxacin [157]. This excessive use of antibiotics is mostly discharged into marine environments, which can be evidenced partially by antibiotic residues detected in fish in Tunisia [158]. Different resistance profiles were also noticed between Vibrio spp. isolated from farmed and wild fish in Tunisia, where Vibrio from wild fish were resistant to amoxicillin and those from aquaculture farming were susceptible to amoxicillin but resistant to the antibiotics colistin and fusidic acid [158]. This was explained by the anomalous use of colistin and fusidic acid antibiotics during the treatment of farmed fish [158]. Similarly, antibiotic resistance in V. alginolyticus isolated from Tunisian aquaculture and conchyliculture farms was relatively higher than that of V. alginolyticus isolated from seawater, rivers and sediments [159]. Antibiotic resistance in marine environments generally exceeds that of terrestrial bacteria [160]. Being exposed to antibiotics over time in the aquatic environment, Vibrio could develop resistance and act as a reservoir of antimicrobial resistance genes. Additionally, some aquatic species such as bivalves could play a role in resistance development, because they can concentrate different bacterial species and antibiotic residues, constituting an excellent setting for the development and exchange of antibiotic resistance [160]. The high resistance rate observed against tetracycline might also be due to the widespread use of tetracycline in aquaculture farms [52]. In the majority of studies, ciprofloxacin retained its effectiveness but reports with notable resistance rates have been emerging [59]. These reports mandate the vigilant use of antibiotics in all ecosystems while adopting a one-health approach to tackle the emergence and dissemination of resistance. Monitoring antimicrobial resistance through antimicrobial susceptibility testing is crucial to gauge the effectiveness of available drugs and new generations of antibiotics. When a high resistance against a molecule is identified within a country, its use becomes uncertain; either in human or veterinary medicine. Similar to non-cholera Vibrio spp., the tracking of antibiotic resistance is also paramount in V. cholerae due to the emergence of resistance through the acquisition of new resistance determinants. The latter is evidenced by the acquisition of MDR IncC-type plasmids by otherwise susceptible isolates in Yemen and Zimbabwe [36,161].

In addition to antibiotic misuse, access to antibiotics and vaccines in the MENA region also contributes to the region's burden. Indeed, reduced access to life-saving antibiotics, especially in countries that are experiencing conflicts and other political turmoil, economic crises and natural disasters, and the increasing incidences of antibiotic-resistant pathogens are predicted to threaten the control and treatment of infectious diseases including vibriosis [162]. Moreover, cholera vaccines are in short supply as reported by the WHO, which led to the temporary suspension of the two-dose vaccination regime in favor of a single-dose strategy during the upsurge in cholera outbreaks in 2022 [163].

Although we highlighted a major need to address the burden of Vibrio in the MENA region, the data discussed in this review have limitations. For example, the Vibrio prevalence range and shifting resistance patterns were extrapolated from selected articles, which might not be exhaustive due to language and database restrictions. The data, in some instances, might also not be readily comparable due to heterogeneities in the analyzed spatiotemporal contexts, study populations, identification methods and antibiotic susceptibility testing procedures.

4. Future perspective

Although this review gives a preliminary overview of the real burden of Vibrio spp. in the MENA region, we are far from fully understanding this burden due to the limited number of studies and the heterogeneities in methods and protocols used for identifying and interpreting antimicrobial susceptibility data. Surveillance of the occurrence of Vibrio spp. in clinical samples should be systematically integrated in the MENA region to provide timely control of outbreaks, while surveys of MDR Vibrio spp. in the aquatic environment should be continuously conducted. In addition to surveillance, health authorities, sanitarians, veterinarians and national and international health organizations are required to enhance the water, sanitation and hygiene infrastructure, secure vaccines for cholera, develop vaccines for non-cholera illnesses associated with Vibrio spp., implement and pursue rigorous management and therapeutic strategies for aquaculture, including using vaccination, probiotics and judicious management of antibiotics and monitoring water quality and feed and seafood safety. These actions could help abate possible threats of Vibrio infections to human health and the environment and curb the rise and spread of multidrug resistance. The latter is critical to low- and middle-income countries and those experiencing poly-crises in the MENA region. It must be emphasized that the rise of antibiotic resistance has more than local ramifications because it does not recognize national borders and could spread across geographical regions.

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17460913.2024.2392460

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