Rapid Demise of Injection Drug Users in the United Kingdom
July 1, 2000 3 minutes read
Rapid Demise of Injection Drug Users in the United Kingdom
abstracts & commentary
Synopsis: An outbreak of soft tissue infection, sepsis, and death in injection drug users in the United Kingdom may be due to infection with Clostridium novyi.
Sources: CDC. MMWR Morb Mortal Wkly Rep 2000;49:489-492; Eastern Regional Health Authority and National Disease Surveillance Centre. Eurosurveillance Weekly, June 22, 2000; http://www.eurosurv.org/update.
Between april 1, 2000, and the third week of june 2000, at least 88 injecting drug users (IDU) were identified with circulatory collapse, pleural effusions, soft tissue edema and necrosis, and evidence of inflammation at the site of drug injection. Forty (45.5%) died.
Twenty-one cases occurred in England and Wales, 48 in Scotland, and the remainder in Ireland. Not all these cases, however, meet the newly agreed upon International Specific Case Definition: "an injecting drug user who has been admitted to hospital or found dead since 1 April 2000 with soft tissue inflammation (abscess, cellulitis, fasciitis, or myositis) at an injection site, and with (i) severe systemic toxicity (sustained systolic blood pressure < 90 mm Hg despite fluid resuscitation and total peripheral white blood cell count > 30 ´ 109/L), or (ii) postmortem evidence of a diffuse toxic or infectious process including pleural effusions and soft tissue oedema or necrosis."
On June 15, the Greater Glasgow Health Board reported that an organism preliminarily identified as Clostridium novyi type A had been isolated from at least six patients. A week later, it was reported that the same organism had been recovered from a patient in Brighton.1,2
Comment by Stan Deresinski, MD
C. novyi causes sudden death in cattle (Black disease) as the result of gas gangrene: "wet, foul smelling lesions." This organism is also involved in 10-40% of human cases of gas gangrene.3 It has also caused, in the absence of gas gangrene, bacteremia, splenic abscess, and other site infections.4
C. novyi type A produces a 250 kDa alpha toxin (CNAT) that acts as a monoglucosyltransferase, catalyzing the incorporation of N-acetylglucosamine into the Rho subfamily proteins.5,6 Rho proteins are a family of GTP-binding proteins involved in the regulation of the actin cytoskeleton, as well as in some signal transduction processes. The acceptor amino acid in Rho, Thr-37, is located in the effector domain of the GTPases and is also the acceptor site for the Clostridium difficile toxins.
CNAT, in fact belongs to a family of large clostridial cytotoxins that includes toxins A and B of C. difficile. Like the C. difficile toxins, with which it has approximately 48% homology, CNAT is cytotoxic in vitro, causing the rounding up of cells as a result of redistribution of the actin cytoskeleton.
Like other clostridia, C. novyi is present in soil and feces. The occurrence of these cases in the United Kingdom suggests a common source of contamination of a supply of heroin. A study reported in 1983 found that 61% of 31 samples of street heroin yielded microbial growth in culture, with the two most commonly isolated organisms being Bacillus sp (79%) and Aspergillus sp (10%).7 They found, however, no correlation between the organisms recovered from the heroin and from soft tissue infections in a group of users.
Soft tissue infection is highly revalent among IDUs, particularly those who inject into muscle or subcutaneous tissues.8 In the United States, and particularly in California, there has been a significant increase in incidences of tetanus, as well as of wound botulism in users of black tar heroin.9,10 Streptococcal fasciitis is another potentially lethal infection encountered in IDUs, but perhaps the most dramatic complication reported in this group was the patient recently encountered in Oslo, Norway, with a subcutaneous abscess, sepsis, and hemorrhagic meningitis from whose cerebrospinal fluid B. anthracis was isolated.11
References
1. Eastern Regional Health Authority and National Disease Surveillance Centre. Eurosurveillance Weekly, 15 June 2000; http://www.eurosurv.org/update.
2. ProMED, 20 June 2000. http://www.fas.org/promed.
3. Caplan ES, Kluge RM. Arch Intern Med 1976;136:788-791.
4. Vleminckx WG, et al. Eur J Gastroenterol Hepatol 1997;9:303-305.
5. Boquet P, et al. Curr Opin Microbiol 1998;1:66-74.
6. Selzer J, et al. J Biol Chem 1996;271:25173-25177.
7. Moustoukas NM, et al. Arch Surg 1983;118:746-749.
8. Binswanger IA, et al. Clin Infect Dis 2000;30:579-581.
9. CDC. Morb Mortal Wkly Rep MMWR 1998;47:149-151.
10. Passaro DJ, et al. JAMA 1998;279:859-863.
11. Høiby EA. Eurosurveillance Weekly 2000:4:000511; http://www.eurosurv.org/2000/0005111.
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