Vibrio Infections 

Vibrio infections are largely classified into two distinct groups: Vibrio cholera infections and noncholera Vibrio infections. Historically, the noncholera Vibrio species are classified as halophilic or nonhalophilic, depending on their requirement of sodium chloride for growth.

Because most Vibrio infections are associated with the consumption of contaminated food, these infections are often considered a foodborne disease. The prevalence of noncholera Vibrio infections in the United States appears to have increased in recent years. The combination of increased water temperature and salinity where shellfish are harvested may contribute to increased contamination rates of shellfish. Although many foodborne diseases are not reportable in the United States, the Centers for Disease Control and Prevention (CDC) estimates that approximately 48 million Americans (or roughly 1 in 6) get sick with foodborne diseases annually. Of these, 128,000 are hospitalized and 3000 die.^[1]

Since 1988, the CDC has maintained a voluntary surveillance system for culture-confirmed Vibrio infections in the Gulf Coast region (Alabama, Florida, Louisiana, Mississippi, and Texas). In 2007, the surveillance was expanded to national notification of infections caused by any Vibrio species. In 2011, the CDC estimates 45,000 cases (90% confidence interval [CI], 23,000-75,000) of Vibrio parahaemolyticus yearly in the United States, 207 cases (90% CI, 138-287) of Vibrio Vulnificus, and 35,000 cases (90% CI, 22,000-52,000) of Vibrio species; this is an estimate owing to underreporting.^[2]

While the estimated incidence of infection with Shiga toxin–producing Escherichia coli O157:H7 (STEC O157) and species of Campylobacter,Cryptosporidium, Listeria,Salmonella, and Yersinia significantly decreased from 1998 to 2010, the incidence of Vibrio infections during this period increased 115% (95% CI, 63%-187%).^[3]

Although Vibrio parahaemolyticus is the most common noncholera Vibrio species reported to cause infection, Vibrio vulnificus is associated with up to 94% of noncholera Vibrio infection-related deaths. Because clinical laboratories do not routinely use the selective medium thiosulfate-citrate-bile salts-sucrose (TCBS) for stool culture, many cases of Vibriogastroenteritis are not identified.^[4]

A review of Cholera and Other Vibrio Illness Surveillance (COVIS) data from 1997-2006 reported that of 4754 Vibrio species–related illnesses, 1210 (25%) were nonfoodborne Vibrio infections (NFVIs).^[5] Of note, the species most frequently isolated in these NFVIs was V vulnificus (35%), followed by Vibrio alginolyticus (29%), and V parahaemolyticus (19%). Not surprisingly, the majority of the reports came from the Gulf Coast region under surveillance (57%), followed by the Atlantic region (24%), the Pacific region (16%), and noncoastal areas (3%). Vibrio was identified in wounds (68%), blood (20%), and “other” (18%).

In the event of a natural disaster, the disturbance to the environment may increase the risk of infectious diseases such as Vibrio infections. During the 2 weeks following Hurricane Katrina in August 2005, the CDC reported 22 new cases of Vibrio infections in Louisiana and Mississippi. V vulnificus accounted for most (82%) of these wound-associated infections.^[6] The increased incidence of Vibrio wound infections in the residents of Gulf Coast states was most likely associated with the exposure of skin and soft-tissue injuries to the contaminated floodwaters.^[6]

The Vibrionaceae family includes the genera Vibrio, Plesiomonas, and Aeromonas. Members of the family Vibrionaceae are natural inhabitants of sea water but can also be found in fresh water. Vibrio species are oxidase-positive, gram-negative bacilli. With the exception of nonhalophilic Vibrio species, such as Vibrio cholerae and Vibrio mimicus, all Vibrio species require saline for growth.

Vibrio species can produce multiple extracellular cytotoxins and enzymes that are associated with extensive tissue damage and that may play a major role in the development of sepsis (see Table 1).

Table 1. Noncholera Vibrio Species and Associated Clinical Presentations (Open Table in a new window)

V vulnificus lives in areas where the temperature exceeds 18°C. In the United States, it is found in the coastal waters of the Gulf of Mexico, New England, and the northern Pacific. Low-to-moderate salinity (15-25 parts per thousand) provides the most favorable growing condition for V vulnificus, and, conversely, high salinity (>25 parts per thousand) adversely affects its survival. Similar to the effect of high salinity, low seawater temperature (< 10°C) significantly inhibits the growth of V vulnificus. V vulnificus is ingested by filter-feeding mollusks such as oysters, mussels, clams, and scallops. During the warmer months, the concentration of bacteria can be as high as 1 X 10⁶ bacteria per gram of oyster.^[7]

Several mechanisms contribute to the virulence of V vulnificus. Iron is an important growth factor. However, because free iron is virtually absent in humans, the organism produces siderophores that acquire iron from transferrin or lactoferrin and deliver it to the bacteria. Conversely, the inability to produce siderophores leads to reduction of virulence. Hepcidin, a natural cysteine-rich peptide, has recently been suggested to possess important antibacterial activity. It is possible that inadequate expression of hepcidin in patients with liver disease predisposes them to serious infections, including those caused by Vibrio species.^{[8, 9]}

Clinical conditions associated with increased free iron, such as hemochromatosis or hemolytic anemia, represent a major risk factor for disseminated Vibrio infections. In addition, V vulnificus produces several other virulence factors, including proteases, hemolysins, and cytolysins. One in particular, a thermolysin-like metalloprotease, activates the bradykinin pathway, causing an increase in vascular permeability. This metalloprotease is far more efficient at activating human enzymes than those of other Vibrio species, possibly explaining why V vulnificus causes severe skin damage and necrotizing fasciitis.^[10]

A recent study in mice, however, has shown that metalloprotease is not necessarily fundamental for the virulence of V vulnificus. The absence of protease activity resulted in increased cytolysin activity that may have contributed to the enhanced virulence.^[11] On animal models, a protease-deficient mutant of V vulnificus was as virulent as the wild-type strain.

The ability of V vulnificus to express a capsular polysaccharide on its cell surface also corresponds to an increased virulence. It allows the bacteria to circumvent the host’s immune system and to cause extensive tissue damage and septicemia. Besides environmental factors such as temperature and aeration, V vulnificus can also alter the amount of capsular polysaccharide displayed on its surface.^[12]

Recently, the gene pyrH has been demonstrated as essential for in vivo survival and growth of V vulnificus in infected mice and is likely associated with its virulence. Clinical isolates of V vulnificus, but not environmental isolates , caused extensive damage to macrophages in animal models, possibly explaining the lethal effects of this infection. PyrH plays a significant role in catalyzing the phosphorylation of UMP to UDP, which is subsequently used in the synthesis of pyrimidines. The numerous attempts to uncover the biochemical profile of pyrH may lead to a novel set of antimicrobial agents.^[13] In addition, photodynamic therapy (PDT) with toluidine blue in mice has been found to be curative in otherwise-fatal V vulnificus wound infections.^[14]

Two major virulence factors in pathogenic V parahaemolyticus strains include a thermostable direct hemolysin (TDH) and a thermostable direct hemolysin-related hemolysin (TRH). TDH induces beta-hemolysis termed the Kanagawa phenomenon on a Wagatsuma blood agar and possesses both enterotoxic and cytotoxic effects, which gives rise to the watery diarrhea associated with V parahaemolyticus infection.^{[15, 16]}

For additional information on cutaneous V vulnificus infections, see the article Vibrio Vulnificus.

Frequency

United States

Between 1998 and 2010, the incidence of Vibrio infections increased by more than 115%. The CDC estimates that 80,000 Vibrio infections (200 V vulnificus, 45,000 V parahaemolyticus, and 35,000 Vibrio species.) and approximately 100 deaths related to Vibrio infections may occur annually in the United States.^[2] Vibrio infections are acquired through consumption of contaminated raw or undercooked shellfish such as oysters, clams, mussels, or crabs. Exposure of wounds to contaminated seawater, injury caused by contaminated seashells, and shark and alligator bites are potential alternative sources of infection (see Table 2).

V parahaemolyticus is the leading cause of seafood-associated gastroenteritis in the United States. During a large outbreak of gastroenteritis in July 2004 in the Gulf of Alaska, V parahaemolyticus caused illness in almost one third of cruise ship passengers who consumed Vibrio -contaminated oysters. From May to July 2006, health departments of New York City, New York state, Oregon, and Washington state reported a total of 177 cases of V parahaemolyticus gastroenteritis. Of these reported cases, 113 (64%) involved residents of Washington state.^[17]

Table 2. Clinical Presentation Rates of Pathogenic Vibrio Infections (Open Table in a new window)

International

Noncholera Vibrio infections are commonly reported in areas such as Japan, Taiwan, China, Hong Kong, Korea, Italy, and Israel. The high prevalence of hepatitis B infections in areas such as China and Taiwan may also contribute to the high incidence of severe noncholera Vibrio infections.

Contrary to epidemiologic patterns of Vibrio infections, only sporadic cases were reported among survivors and injured individuals following the tsunami that devastated Thailand, Indonesia, and India in December 2004.

Despite a high annual estimated incidence of V vulnificus septicemia in Japan (425 cases; 95% CI, 238-752), a survey of registered emergency physicians in Japan surprisingly revealed that only 15.7% (95% CI, 11.3-21.0) of responding physicians had a basic knowledge of this frequently fatal infection.^[18]

Mortality/Morbidity

According to CDC estimates, foodborne diseases cause approximately 48 million illnesses, 128,000 hospitalizations, and 3000 deaths annually in the United States.^[1]

Foodborne noncholera Vibrio infections may occur at rate of 0.2-0.3 case per 100,000 population. In 2011, CDC estimates 45,000 cases of V parahaemolyticus infection annually, resulting in 129 hospitalizations (90% CI, 66-219) and 5 deaths (90% CI, 0-22). Two hundred and seven cases of V vulnificus infection are estimated to occur annually (90% CI, 138-287), resulting in 200 hospitalizations (90% CI, 120-303) and 77 deaths (90% CI, 43-120).^[2]

Although Vibrio infections are not as common as Campylobacter, Salmonella, or Listeria infections, more patients with Vibrio infections die because of the high mortality rate (35-50%) associated with V vulnificus septicemia.

Among all foodborne diseases, V vulnificus infection is associated with the highest case fatality rate (39%).

Patients with cirrhosis who consumed raw oysters were 80 times more likely to develop V vulnificus infection and 200 times more likely to die of the infection than those without liver disease who consumed raw oysters.^[19]

Regardless of pre-existing conditions, the mortality risk increases in patients with V vulnificus infection who are hospitalized more than two days after symptoms develop (OR, 2.9; 95% CI, 1.8-4.8).^[20]

A delay in performing the first fasciotomy (>24 h) after development of clinical symptoms in patients with V vulnificus necrotizing fasciitis was associated with 5-fold increase in the mortality risk.

Race

Vibrio infections have no racial predilection. Because Vibrio species are natural inhabitants of sea water, Vibrio infections are more commonly reported in states or countries bordered by large bodies of sea water. Persons with underlying medical conditions, such as alcoholism, cirrhosis, or malignancy, and recipients of organ transplants are at increased risk of Vibrio infections and serious complications. Patients with end-stage renal failure who are on continuous ambulatory peritoneal dialysis (CAPD) may develop peritonitis after eating or handling raw sea fish.

Sex

Vibrio infections can occur in all persons, regardless of sex. V vulnificus infections were reported in women who engaged in sexual intercourse in brackish water of the Gulf of Mexico. In general, V vulnificus infections are more common in males (82%), according to most reports.

Age

Persons of any age who consume or are exposed to Vibrio- contaminated food or water are at risk of developing Vibrio infection, especially if they have underlying medical conditions such as advanced liver disease.

Most patients with Vibrio wound infections and septicemia are aged 50-60 years.