By: Claudia Mangiola, Daniel Moses and Janina Ruffini
Vibrio vulnificus is a Gram-negative bacterium responsible for the majority of seafood-associated deaths in the United States. As a natural inhabitant of warm oceans and estuaries, it is found in high concentrations in shellfish such as oysters and clams, which serve as the source of transmission when consumed or exposed to wounds. Incidences of V. vulnificus generally occur as isolated cases, although outbreaks affecting multiple states have been reported.
Three biotypes with identical genotypes of pathogenic V. vulnificus have been identified and classified according to their biochemistry. Biotype 1 strains are found in salt water worldwide and are therefore the most common. They present the greatest concern to human health due to their large spectrum of symptoms and high mortality rate. Biotypes 2 and 3 are associated with farmed eels and freshwater fish in the Middle East and rarely cause severe infection in humans. The presence of V. vulnificus does not affect the taste or odor of contaminated seafood, making detection challenging. Consumption of this seafood results in gastroenteritis (inflammation of the stomach and intestines) accompanied by fever as well as septicemia (blood infection). Individuals with septicemia develop a fever, abdominal pain, hypotension and skin lesions on their extremities. This condition develops in 1 week and is fatal in up to 60% of cases. Handling contaminated seafood and exposing wounds to water containing V. vulnificus can cause skin infections. Patients with wound infections typically have a pre-existing lesion. The wound inflames and becomes very painful however they have a lower mortality rate. Necrotizing fasciitis, being the most severe form, is characterized by black bulbous protrusions, patchy discoloration, and scalding of the skin, similar to that caused by Streptococcus pyogenes depicted in figure 1. V. vulnificus infection can be diagnosed by detecting edema in the radiography of tissues and by performing blood cultures and Gram stains from lesions.
Figure 1. This man’s leg is severely infected causing necrotizing fasciitis. It shows hemorrhagic bullae (black bulbous protrusions), patchy discoloration, and scalding of the skin. Surgery was necessary to help clear the infection. Source: Smuszkiewicz, 2008.
V. vulnificus is more prevalent in the USA along the coastline of the Gulf of Mexico. While bacteria can survive in water temperatures between 9℃ – 31℃, they prefer warmer waters above 18℃, predominantly in the months between April-October. Infection occurs from ingestion of uncooked contaminated seafood such as oysters. Of those infected, there is a 40-60% mortality rate, mostly caused by septicemia. The CDC estimates that infection rates are over 200 cases per year. Although a more rare disease, risk factors prior to infection include alcoholism, primary septicemia, liver disease and any chronic diseases.
Infection of V. vulnificus results in symptoms within 24 hours. That being said, the bacterium is able to evade the immune response and cause disease very quickly due to its virulence factors. Virulence factors are molecules produced by bacteria which help to colonize a host, or help it evade the host’s immune system allowing it to persist and cause damage. The virulence factors of V. vulnificus allow bacteria to survive acidic environments, evade the innate immune response and acquire nutrients from the environment. This is accomplished through the polysaccharide capsule and an iron acquiring mechanism unique to V. vulnificus.
Once the bacterium enters the bloodstream, the innate immune system responds with the protein complex referred to as complement proteins. These will bind to the bacterium and cause an immune cell to engulf it. This is actually avoided in V. vulnificus because of the polysaccharide capsule which does not allow these proteins to bind, thus avoiding being taken up by macrophages (immune cells) (Figure 2). Another essential virulence factor is iron acquisition. This has been shown to enhance growth and to compromise the immune response. This is accomplished through a unique mechanism in V. vulnificus which uses a protein encoded in its genome that take iron from red blood cells. V. vulnificus has the ability to regulate these virulence factors with quorum sensing, which is the up or down regulation of gene expression in response to cell density and sensory signals. Quorum sensing is used to control gene expression of proteins that acquire iron from red blood cells.
Figure 2. This is a cell of V. vulnificus shown with its many virulence factors. The complement system and macrophages do not have any effect on the invading cells because of the polysaccharide capsule. Also shown are the siderophores for iron acquisition, pili for adhesion and colonization, the flagella for motility, the heme receptor and lipopolysaccharides (LPS) on Vibrio’s surface. Source: Janina Ruffini.
Treatment and Prevention
Treatment of V. vulnificus is strongly dependent on the type of infection, whether it is septicemia, a wound infection, or gastroenteritis. A variety of antibiotics have been shown to be effective against V. vulnificus. These are given orally and intravenously in certain combinations. It is imperative that people who suspect a V. vulnificus infection seek immediate help for septicemia since survival is dependent on how quickly treatment is received.
In cases of wound infections, antibiotics are usually ineffective because of thrombosis (clots) in the blood vessels near the infection site, and the antibiotics do not reach the infected tissues. Often surgery is required to remove the bacterial burden and damaged tissues, sometimes even amputation of limbs is necessary to save the patient.
Gastroenteritis, unlike septicemia and wound infections, often goes unreported. Symptoms include fever, diarrhea, abdominal cramps, nausea, and vomiting but tends to resolve itself. Replacement of fluids and rest are the ideal treatment in this case.
The CDC has reported a list of preventative measures one can take to avoid V. vulnificus infection, which boils down to cooking shellfish thoroughly.
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