A "fishy remedy": an unusual transmission of Vibrio vulnificus infection.

Abstract: This case report describes a unique transmission of Vibrio vulnificus infection. A 38-year-old woman with recurrent cellulitis and chronic ulcer on her leg developed necrotizing cellulitis and sepsis caused by V. vulnificus. Meticulous history investigation revealed the link to contaminated fish blood that had been applied on the ulcer by a traditional healer. Through this case, it may be stressed that a traditional remedy can sometimes be harmful and life-threatening.

Key Words: necrotizing cellulitis, traditional remedy, Vibrio vulnificus

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Vibrio vulnificus is an invasive Gram-negative bacillus found in marine and freshwater fish that may cause gastroenteritis, necrotizing cellulitis, bacteremia, and sepsis. Skin infections are caused by penetration of the organism through preexisting skin lesions or through lesions incurred during seawater-related activities, such as cleaning fish or shucking oysters. (1), (2) We report a unique case of V. vulnificus necrotizing cellulitis and sepsis as a result of the application of fish blood on an ulcer as a traditional remedy.

Discussion

We describe the first case of V. vulnificus cellulitis and sepsis, after the direct application of fish blood on a chronic leg ulcer. V. vulnificus is a pathogenic Gram-negative bacterium, endemic to brackish waters, that is often isolated from sediments, from the water column, or from shellfish. It is associated with wound infections and septicemia in humans. Virulence is associated with the presence of a polysaccharide capsule that probably contributes to the ability to resist phagocytosis and the killing effects of human serum. (3), (4) Strains of V. vulnificus produce multiple toxins including collagenase and cytolytic and proteolytic substances containing mucinase, protease, lipase, deoxyribonuclease, chondroitin sulfate, and hyaluronidase, which are associated with extensive tissue damage and may play a major role in the development of sepsis. (5) Underlying hepatic illnesses, such as cirrhosis, alcoholism, hemochromatosis, and immunosuppression, are important factors contributing to the severity of the infection and outcome. (6), (7) The development of cellulitis on the extremities of people through occupations or recreation related to seawater or marine animals is well known and should suggest V. vulnificus (especially in the presence of severe necrotizing cellulitis) or rarely V. alginolyticus. (8)

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Wound infections caused by V. vulnificus generally occur in persons without any chronic illness; 35 to 60% of patients with wounds may become bacteremic, and 25% of those with bacteremia secondary to wound infections may die as a result of their infection. (1), (9) Patients often present with fever, pain, and swelling at the wound site, and cellulitis. The skin and soft tissue infection can progress rapidly from simple erythema to cellulitis, necrotizing fasciitis, and myositis. Once necrotizing fasciitis or cellulitis is suspected, Gram stains of cultures that display curved bacilli with or without pleomorphic forms should be regarded as suggestive of the presence of Vibrio organisms. Because of the invasiveness of wound infections, debridement of infected wounds is generally recommended to avoid limb amputation. (5), (10)

Most cases of V. vulnificus infection are sporadic, and no common-source outbreaks have been described. Before 1996, infections caused by V. vulnificus were very rare in Israel. Between May 1996 and December 1997, an outbreak (62 cases) of invasive V. vulnificus infection, wound infection, and bacteremia occurred in Israel. It was associated with exposure to pond-cultivated fish and caused by a newly identified virulent clone of V. vulnificus that was designated as V. vulnificus biogroup 3 by the Centers for Disease Control and Prevention. During this period, fishpond managers initiated a new marketing policy, in which fish were sold alive instead of being packed in ice. These changes resulted in an increased survival of the bacterium and more injuries from fish fins. (11)

Similar to other vibrios, V. vulnificus may be overlooked if plated on nonselective medium. This may explain the laboratory error in the early misidentification of the Gram-negative organism as Pseudomonas in our case.

V. vulnificus and Vibrio alginolyticus grow readily on standard media that contain sodium chloride (eg, MacConkey agar) and the selective thiosulfate-citrate-bile salts-sucrose medium, and differential diagnosis between these two Vibrio species may be difficult. (8) Biochemical tests alone can not easily distinguish between V. alginolyticus and V. vulnificus biogroup 3, because the automated system does not recognize subtypes of the same species. The presence of the V. vulnificus cytotoxin gene by PCR established the final identification. (12)

In the present case, V. vulnificus infection was not suspected at first. Blood cultures were performed because of the development of fever and cellulitis. When, 24 hours later, two of the cultures grew a curved Gram-negative rod, which was finally identified as V. vulnificus, repeated history revealed the link to fish blood, as the patient recalled that her leg had been sprayed with fresh fish blood in an attempt to treat her chronic ulcer.

Traditional remedies often have no scientific basis other than as a placebo. Although some traditional remedies may be of benefit, many of them have little or no effect. Through our patient, it may be stressed that this kind of treatment can sometimes be harmful and life-threatening.

Conclusions

We present a unique case of V. vulnificus transmission. For various reasons, patients do not always reveal all the pertinent details. Moreover, when physicians and patients encounter a recurrent pattern of a disease that is familiar to both patient and physician, they may overlook important clues for an unusual presentation. Due to the high fatality rate in cases in which Vibrio sepsis is involved, a meticulous history investigation is recommended for all cases of cellulitis, even those that are recurrent. Questions directed to any recent exposure to seawater or marine animals could provide an important clue to the correct diagnosis.

Key Points

* Vibrio bacteria may be overlooked if plated on non-selective medium.

* A meticulous history investigation is recommended for all cases of cellulitis.

* Traditional remedies can sometimes be harmful and even life-threatening.

Accepted June 25, 2003.

Copyright [c] 2004 by The Southern Medical Association 0038-4348/04/9702-0205

References

(1.) Klontz KC, Lieb S, Schreiber M, et al. Syndromes of Vibrio vulnificus infections: Clinical and epidemiologic features in Florida cases, 1981-1987. Ann Intern Med 1988;109:318-323.

(2.) Hlady WG, Klontz KC. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 1996;173:1176-1183.

(3.) Reddy GP, Hayat U, Xu Q, et al. Structure determination of the capsular polysaccharide from Vibrio vulnificus strain 6353. Eur J Biochem 1998;255:279-288.

(4.) Yoshida S, Ogawa M, Mizuguchi Y. Relation of capsular materials and colony opacity to virulence of Vibrio vulnificus. Infect Immun 1985;47:446-451.

(5.) Daniels NA, Shafaie A. A review of pathogenic Vibrio infections for clinicians. Infect Med 2000;17:665-685.

(6.) Kizer KW. Vibrio vulnificus hazard in patients with liver disease. West J Med 1994;161:64-65.

(7.) Bullen JJ, Spalding PB, Ward CG, et al. Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch Intern Med 1991;151:1606-1609.

(8.) Carpenter C. Other pathogenic vibrios, in Mandell GL, Bennett JE, Dolin R (eds): Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. New York, Churchill Livingstone, 1995, ed 4, pp 1945-1948.

(9.) Howard RJ, Lieb S. Soft-tissue infections caused by halophilic marine vibrios. Arch Surg 1988;123:245-249.

(10.) Janda JM. A lethal leviathan: Vibrio vulnificus. West J Med 1991;155:421-422 (editorial).

(11.) Bisharat N, Agmon V, Finkelstein R, et al. Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel: Israel Vibrio Study Group. Lancet 1999;354:1421-1424.

(12.) Stelma GN Jr, Reyes AL, Peeler JT, et al. Virulence characteristics of clinical and environmental isolates of Vibrio vulnificus. Appl Environ Microbiol 1992;58:2776-2782.

RELATED ARTICLE: Case Report

A 38-year-old woman was admitted from another hospital with recurrent erysipelas and chronic ulcer on her left leg. Her medical history was significant for obesity, microcytic anemia, and recurrent erysipelas with a chronic ulcer of the left leg for the past 3 years. She did not smoke, drink alcohol, or use illicit drugs. The patient had no history of liver disease, hemochromatosis, diabetes, or immunosuppression. She had been well until 3 days earlier, when an abrupt onset of severe pain, swelling, and tenderness of the left leg associated with malaise, rigors, and systemic fever developed. The patient was hospitalized with a diagnosis of recurrent erysipelas of the left leg; blood cultures were obtained and treatment with IV cefazolin at 1 g administered three times per day was started. Doppler studies showed intact pulses in the lower extremities, without evidence of deep venous thrombosis. The next day, the patient was transferred to our hospital.

Physical examination revealed a morbid obese woman in mild distress from lower extremity pain. Her temperature was 37.8[degrees]C, her respiratory rate was 20 breaths/min, her pulse was 110 beats/min, and her blood pressure was 100/55 mm Hg. The patient was alert and oriented. Findings from the patient's heart, lung, and abdomen were unremarkable. There was a notable left calf deep ulcer, measuring 3 X 2 X 3 cm, with elevated margins and surrounding erythema. The entire left leg was swollen and the area around the wound was tender to palpation. Findings from a chest x-ray and an electrocardiogram were unremarkable.

Laboratory studies at admission were as follows: hemoglobin, 8.4 g/dl; hematocrit, 25.2%; mean corpuscular volume, 73.3 fl; platelet count, 293 X 1[0.sup.3]/[micro]l; white blood cell count, 14.6 X 1[0.sup.3]/[micro]l, with a left shift; and erythrocyte sedimentation rate, 157 mm/h. Her serum glucose was 64 mg/dl, her serum urea nitrogen was 43 mg/dl, her creatinine was 2.4 mg/dl, and her albumin was 2.8 mg/dl. The electrolyte, levels of liver enzymes, and bilirubin were within normal limits.

During the following 24 hours, the patient remained febrile, complaining of increasing pain and numbness over the left calf. After adequate hydration, creatinine and serum urea nitrogen returned to the normal range. The physical signs progressed further, with formation of hemorrhagic bullae, thrombosis of superficial veins, and skin necrosis (Fig. 1). At that time, blood cultures were reported as growing an oxidase-positive Gram-negative bacillus. Pseudomonas aeruginosa infection was suggested, and antibiotics were changed to IV ciprofloxacin 400 mg administered twice daily. However, 24 hours later, the bacterium was identified as Vibrio spp., probably V. alginolyticus.

Ceftazidime 2 g administered three times per day was started and the patient was transferred immediately to an orthopedic department. The patient had three surgical debridements of necrotic tissue, and graft implantation was performed. She was discharged from the hospital after 3 months and recovered completely.

After we received the final identification of the bacteria, we returned to question the patient regarding whether she had had any contact with the sea or fish before this illness. The patient was surprised by the question and responded by asking us, "How did you know?" Then, she recalled that 3 days previously she had been advised to see a traditional folk healer for the chronic ulcer in her left lower extremity. The healer, a 100-year-old woman, was well known in the area for treating patients by means of traditional remedies; in this case, she sprayed fresh fish blood on the site of the ulcer area. The healer bandaged her leg and told her not to wash for 3 days.

Because V. alginolyticus sepsis is very rare, and because confusion may arise in the identification of Vibrio isolates, we also performed polymerase chain reaction (PCR) for the presence of the V. vulnificus cytotoxin gene. We obtained a final report, with PCR identification of the causative agent as V. vulnificus.

Sari Tal, MD, Vladimir Guller, MD, Oren Zimhony, MD, Shmuel Levi, MD, Mrina Greenshpun, MD, and Alexander Gurevich, MD

From the Subacute Department, Harzfeld Geriatric Hospital, and the Infectious Diseases Unit, Kaplan Medical Center, Rehovot, Israel, affiliated with the Hebrew University Medical School, Jerusalem, Israel.

Reprint requests to Sari Tal, MD, Subacute Department, Harzfeld Geriatric Hospital, Kaplan Medical Center, Gedera 70750, Israel. Email: [e-mail]