Version May 2024
INTRODUCTION — Vibrio parahaemolyticus is a gram-negative bacterium that can cause seafood-associated diarrheal illness; it has also been associated with wound infections and septicemia [1,2].
V. parahaemolyticus was first isolated in 1950 from clinical samples and "shirasu" (dried sardines) during an outbreak of gastroenteritis in Osaka, Japan. It was the leading cause of foodborne illness in Japan for many years, although implementation of aggressive control measures has resulted in a substantial drop in its incidence in Japan [3-5]. However, it remains a frequent global cause of diarrhea in areas where seafood consumption is common [6,7]. In the United States, V. parahaemolyticus is the most common Vibrio-associated cause of foodborne illness (table 1). It also causes illness in a number of seafood species; in shrimp, it causes acute hepatopancreatic necrosis disease, which has important economic consequences [8].
The pathogenesis, epidemiology, clinical features, diagnosis, and treatment of V. parahaemolyticus infections will be reviewed here. Vibrio vulnificus, other "non-cholera" Vibrios, and Vibrio cholerae are discussed separately. (See "Vibrio vulnificus infection" and "Cholera: Epidemiology, clinical features, and diagnosis" and "Infections due to non-O1/O139 Vibrio cholerae".)
PATHOGENESIS — The pathogenicity of V. parahaemolyticus has been correlated with production of thermostable direct hemolysin (Vp-TDH), which is responsible for the beta-hemolysis observed when the organisms are plated on a modified blood agar (Wagatsuma agar) [9]. This is known as the Kanagawa phenomenon, named after the region in Japan where it was discovered.
The Kanagawa phenomenon was originally demonstrated in 96 percent of Japanese clinical isolates but in only 1 percent of environmental strains. In one study of human volunteers, Kanagawa-positive strains produced diarrhea, while Kanagawa-negative strains did not (even in doses of up to 10(9) organisms) [10]. Deletion of the Vp-TDH gene results in loss of enterotoxic activity in laboratory models [11].
A second group of hemolysins, known as Vp-TDH-related hemolysins (Vp-TRH), can be found in certain clinical isolates of V. parahaemolyticus. Many of these strains are phenotypically Kanagawa negative. Along the Pacific coast of the United States and in parts of Asia, there have been case clusters associated with V. parahaemolyticus strains that are urease positive but Kanagawa negative [12,13]. These strains have almost always been shown to carry the genes for Vp-TRH [14,15].
Although the majority of clinical isolates produce Vp-TDH and/or Vp-TRH, in one study 6 percent of clinical samples lacked both toxin genes, suggesting the presence of additional virulence factors [16]. Genomic studies have shown that some V. parahaemolyticus strains carry genes for the type III secretion system, which has been linked with pathogenicity in other diarrheal pathogens (eg, Shigella spp, Salmonella spp, enteropathogenic Escherichia coli, and other non-cholera Vibrios) [17-20]. Strains have also been shown to carry genes of the type VI secretion system [21]. These systems may represent additional virulence factors, possibly associated with a more invasive type of diarrhea due to V. parahaemolyticus.
EPIDEMIOLOGY — Like other Vibrios, V. parahaemolyticus exists as a free-living bacterium in estuarine or marine environments and is a common seafood contaminant. Counts of the bacterium in the environment (and in oysters) tend to increase as water temperatures rise, making this a microorganism that is particularly susceptible to the effect of global warming [22-25]. Bacterial counts may also be influenced by salinity; higher counts have been observed in regions of lower salinity [26].
There was a global increase in the incidence of V. parahaemolyticus infections beginning in the mid-1990s, associated with the appearance of a new pandemic variant [27]. Isolates in this group have a high degree of genetic similarity, albeit with a diversity of serotypes, including O3:K6, O4:K68, and O1:K untypable (O1:KUT) [28-31]. These isolates were first identified on the Indian subcontinent and subsequently have been identified in clinical and environmental samples from all continents [32-35]. They appeared in the late 1990s/early 2000s along the western coast of South America, in an expansion reminiscent of the appearance of V. cholerae El Tor in South America in 1991. In both instances, spread of the pandemic microorganism from Asia to South America occurred in the setting of an El Nino weather event [36]. An epidemic involving a sequence type (ST)-120 strain was reported in 2009, with genetic data again implicating Asia as the source [37]. Beginning in 2016, a new variant, 04:KUT-recAin, began to emerge in China, where it has become the main epidemic strain [38].
In the United States, reports from surveillance programs suggest that the incidence of Vibrio infections is increasing, from 0.01 to 0.06 per 100,000 persons in 1996 to an estimated 0.39 cases per 100,000 in 2015 [39]. By 2019, the incidence had increased to 0.9 cases/100,000 population [40]; however, this increase was associated with a significant increase in diagnoses by culture-independent methods, making it difficult to distinguish the actual increase in incidence from improved clinical laboratory diagnostic techniques.
V. parahaemolyticus is most commonly transmitted by contaminated seafood. In the United States, V. parahaemolyticus has been responsible for a number of major food-borne disease outbreaks, often involving mishandling and/or cross-contamination of seafood after cooking. Commonly implicated vehicles include oysters, clams, shrimp, crab, and, in one study in coastal areas of Texas and Louisiana, cooked crayfish [22,41-43].
Wound infections are most often associated with marine recreational activities (swimming, shore walking, boating) and, less commonly, with handling of seafood [44-46].
CLINICAL MANIFESTATIONS — V. parahaemolyticus most commonly causes gastroenteritis, characterized predominantly by diarrhea; a smaller percentage have wound infections. Bacteremia can also occur, particularly in patients with underlying conditions such as liver disease. Fifteen percent of reported case patients in the United States in 2014 were hospitalized, and 1 percent died.
Gastroenteritis — In a case series of 345 sporadic V. parahaemolyticus infections in the United States, clinical manifestations of patients with gastroenteritis included diarrhea (98 percent), abdominal cramps (89 percent), nausea (76 percent), vomiting (55 percent), and fever (52 percent) [42]. Bloody diarrhea has been reported in up to 29 percent of cases in some series [47,48]. Based on data from food-borne outbreaks, the median incubation period for gastroenteritis is 17 hours (range 7 to 72 hours) [49], with a median reported duration of illness of 2.4 days (range, 8 hours to 12 days) [42]. Somewhat milder symptomatology was reported in an oyster-associated outbreak in Alaska: fever (34 percent), vomiting (29 percent) and bloody diarrhea (7 percent); the median duration of symptoms was 5 days [23].
Wound infections — Wound infections associated with exposure of wounds to estuarine waters are generally mild. However, for patients with underlying conditions such as liver disease, alcoholism, or diabetes, cellulitis can be severe, with a reported 3 percent case fatality rate [42,44].
Bacteremia — V. parahaemolyticus can also cause septicemia, particularly in individuals with underlying liver disease (as also reported with other Vibrios). In a report of 17 patients with V. parahaemolyticus septicemia, the case fatality rate was 29 percent [42]. Among the 11 patients with sepsis for whom food histories were available, 10 (91 percent) had eaten raw oysters before the onset of illness. (See "Infections due to non-O1/O139 Vibrio cholerae" and "Vibrio vulnificus infection".)
DIAGNOSIS — V. parahaemolyticus grows well on blood agar and other nonselective media. Isolation from stool in laboratories employing classic microbiological methods generally requires use of a selective culture medium, such as Thiosulfate Citrate Bile-salts Sucrose (TCBS). V. parahaemolyticus does not ferment sucrose; consequently, colonies on TCBS are blue-green in color. Species identification is based on standard biochemical tests. The laboratory should be alerted regarding cases in which V. parahaemolyticus is suspected so that the appropriate diagnostic techniques can be implemented.
However, in the United States, the number of clinical microbiology laboratories using classic methods is decreasing, with the United States Centers for Disease Control and Prevention FoodNet data suggesting that approximately 56 percent of Vibrio diagnoses in 2022 were made with molecular or other culture-independent tests [50]. Because culture-independent methods do not require special selective media for isolation or advance notification of a suspect case, their use is likely to increase the number of V. parahaemolyticus infections diagnosed.
Most environmental V. parahaemolyticus isolates lack the genes necessary to cause illness in humans (see 'Pathogenesis' above). Clinically significant isolates are hemolytic (have a positive Kanagawa reaction) or have a positive urease reaction. Confirmation that a strain is pathogenic has traditionally required use of polymerase chain reaction to confirm the presence of thermostable direct hemolysin (TDH) and/or TDH-related hemolysin (TRH) genes [51], a procedure which has generally only been available in state reference laboratories. With increasing use of culture-independent diagnostic methods, commercial tests specific for TDH and TRH may become more widely available.
TREATMENT
Gastroenteritis
Supportive care — Volume repletion is the most important element of therapy in patients with Vibrio gastroenteritis. The gastroenteritis caused by V. parahaemolyticus tends to be mild and self-limited. Antimicrobial therapy is reasonable in more severe cases, since among patients with cholera, antibiotic therapy is known to decrease the duration of diarrhea and the excretion of infectious organisms. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings" and "Maintenance and replacement fluid therapy in adults".)
Antimicrobial therapy — There are no controlled trials of therapy for gastroenteritis due to Vibrio parahaemolyticus. Therefore, antimicrobial therapy is guided by the same principles used for comparable clinical syndromes caused by other Vibrio species. Based on clinical trials in cholera and in vitro susceptibility data, doxycycline is a reasonable antibiotic choice; reasonable alternatives include fluoroquinolones and macrolides. The duration of therapy depends on the antibiotic chosen, as outlined separately for cholera. (See "Cholera: Epidemiology, clinical features, and diagnosis".)
Mild wound infections — Wound infections require debridement and antimicrobial therapy. Mild wound infections in patients who do not have significant underlying diseases generally respond well to local wound care and oral antibiotics (such as a tetracycline or a fluoroquinolone). This approach is guided by the same principles used for comparable clinical syndromes caused by V. vulnificus. Duration of therapy is dictated by clinical response; most patients respond to five to seven days of antibiotics. (See "Vibrio vulnificus infection", section on 'Treatment'.)
Bacteremia or severe wound infections — Patients with septicemia or wound infections in the setting of risk factors for septicemia require aggressive antimicrobial therapy, frequently in an ICU setting.
We suggest antimicrobial treatment with a tetracycline plus a third-generation cephalosporin. Appropriate combination regimens include either minocycline or doxycycline (100 mg orally twice daily), plus either cefotaxime (2 g intravenously every eight hours) or ceftriaxone (1 g intravenously daily). Depending on clinical response and the degree of the patient's immunosuppression, two weeks (or more) of antimicrobial therapy may be necessary.
No controlled trials have evaluated optimal therapy for V. parahaemolyticus sepsis or severe wound infections. Support for these treatment regimens comes primarily from studies evaluating therapy of V. vulnificus infections. (See "Vibrio vulnificus infection", section on 'Treatment'.)
PREVENTION — As with all Vibrios, risk of infection may be reduced by avoiding consumption of raw or undercooked shellfish, particularly during warm, summer months. Postharvest treatments (mild heat treatment, freezing, hydrostatic pressure) can reduce V. parahaemolyticus counts in raw oysters, potentially reducing disease risk [52]. Care must also be exercised to minimize mishandling of fish and shellfish and to avoid cross-contamination of cooked foods by raw seafood.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
SUMMARY AND RECOMMENDATIONS
●Vibrio parahaemolyticus is a gram-negative bacterium that can cause seafood-associated diarrheal illness; it has also been associated with wound infections and septicemia. Gastroenteritis often occurs in the setting of mishandling and/or cross-contamination of seafood after cooking. In these cases, clinical manifestations include diarrhea, abdominal cramps, nausea, vomiting, and fever. Wound infections associated with exposure of wounds to estuarine waters can be severe in the setting of liver disease, alcoholism, or diabetes. V. parahaemolyticus can also cause septicemia, particularly in individuals with underlying liver disease (as with other Vibrios). (See 'Introduction' above and 'Clinical manifestations' above and 'Epidemiology' above.)
●The pathogenicity of V. parahaemolyticus has been correlated with production of thermostable direct hemolysin (Vp-TDH), which is responsible for the beta-hemolysis observed when the organisms are plated on a modified blood agar (Wagatsuma agar). This is known as the Kanagawa phenomenon, named after the region in Japan where it was discovered. A second group of hemolysins, known as Vp-TDH-related hemolysins, or Vp-TRH, can be found in certain clinical isolates of V. parahaemolyticus. Many of these strains are phenotypically Kanagawa negative. (See 'Pathogenesis' above.)
●V. parahaemolyticus grows well on blood agar and other nonselective media. Gastrointestinal infections are probably best identified using culture-independent methods. For laboratories still using traditional culture-based approaches, isolation of V. parahaemolyticus from stool requires use of a selective medium, such as Thiosulfate Citrate Bile-salts Sucrose. Clinically significant isolates are hemolytic (have a positive Kanagawa reaction) or have a positive urease reaction. (See 'Diagnosis' above.)
●Volume repletion is the most important element of therapy in patients with Vibrio gastroenteritis. The gastroenteritis caused by V. parahaemolyticus tends to be mild and self-limited. More severe cases benefit from antimicrobial therapy; we suggest treatment with doxycycline (Grade 2C). (See 'Treatment' above.)
●Treatment of wound infections requires debridement and antimicrobial therapy. We suggest a tetracycline or fluoroquinolone for treatment of mild wound infections in patients who do not have risk factors for serious infection (Grade 2C). (See 'Treatment' above.)
●Treatment of septicemia or wound infections in the setting of risk factors for septicemia requires aggressive antimicrobial therapy; intensive care management may also be needed. We suggest antimicrobial treatment with a tetracycline plus a third-generation cephalosporin (Grade 2C). (See 'Treatment' above.)
●Risk of infection may be reduced by avoiding consumption of raw or undercooked shellfish, particularly during warm, summer months. Postharvest treatments (mild heat treatment, freezing, hydrostatic pressure) can reduce V. parahaemolyticus counts in raw oysters, potentially reducing disease risk. Care must also be exercised to minimize mishandling of fish and shellfish and to avoid cross-contamination of cooked foods by raw seafood. (See 'Prevention' above.)
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