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In April to June 2000 an outbreak of unexplained illness in injecting drug users (IDUs) in parts of the UK led to hospitalisation and usually death among those affected.1 For investigation purposes a new syndrome-based case definition was constructed as, extensive inflammation at a subcutaneous or intramuscular injection site and, either severe system toxicity or, postmortem evidence of a diffuse toxic or infectious process.2 Between 1 April and 19 June investigation of 88 hospitalised or dead IDUs with injection site soft tissue inflammation found 35 met the case definition. Despite very high mortality (34, 97%) only limited epidemiological information is available.1 However, empirical evidence identifying the characteristics of IDUs most at risk is fundamental to, better understanding the outbreak, preventing re-occurrence and developing appropriate advice should one occur in the UK or elsewhere.
By the end of June, 14 confirmed cases (12 fatal) were identified in the north west of England; the area with the majority of English cases1 and historically a high prevalence of injecting drug users.3 Based on these cases, we present results from a case-control study that provides the first empirical information on IDUs most at risk.
Methods and Results
As most cases had died, the Regional Drug Misuse Databases (RDMDs)4 5 were used to develop retrospective case (and control) histories on demographics and drug use. The North West RDMDs collect information on drug users combining data from diverse settings including; treatment services, police, prisons, and probation.4 5 Datasets do not store names but use anonymised identifiers (initials, birth date, sex, and a geographical marker). Using these, exact matches for 12 of the 14 cases were located on the databases and data from their most recent contact extracted (police surgeons n=2, community drug teams n=8, drug dependency unit=1, prison medical service n=1). Most (75%) cases had been seen within the past three years. For each case 10 controls were randomly selected from individuals attending the same agency within a period of ± six months. Identical data fields were extracted for controls and cases. All analyses were undertaken separately for each factor first without matching and then, using logistic regression and including a field linking each case to their controls.
Cases were significantly more likely to be female than controls (table1) and were more than three years older (mean age 33 on 1 April 2000). Furthermore, duration of heroin use was 4.22 years greater for cases. At last presentation to services cases were more likely to be currently injecting (that is, injected in the previous four weeks) and of all injectors, cases were more likely to have shared needles. Furthermore, among benzodiazepine users, cases had higher levels of injecting benzodiazepines, indicative of more chaotic behaviour.
Using an established multi-agency drug database we have identified demographics and drug use risk factors for the recent unexplained illness affecting IDUs in the UK. Cases were more likely (than controls) to be female. Half of cases in this study and 49% of all cases identified across the UK were female1 (compared with 30% women RDMDs4). Among injectors, cases also had higher levels of having shared needles and having injected benzodiazepines; indicative of more chaotic behaviour.
The most probable cause of this unexplained syndrome isClostridium novyi infection; an anaerobic bacteria more likely to flourish in subcutaneous or intramuscular injection sites.1 Prolonged injecting drug use, especially including benzodiazepine, can lead to venous damage while injecting cocaine constricts the blood vessels. Respectively, these factors promote a greater likelihood of accidental or intended non-venous injection and reduced oxygen to blood vessels when venous injection occurs. Both factors are likely to aid growth of anaerobic bacteria. Furthermore, women have more difficulty accessing superficial veins.6
Critically, prevention and identification of further cases relies on better understanding of this condition. Extensive field studies being undertaken in Glasgow should elaborate more details of risk. In the meantime however, this study provides the first evidence of additional risk from this unexplained illness to women, older drug users and those with more chaotic injecting histories.
This report has relied on the cooperation of a wide variety of agencies including drug services, police, and prisons. We thank them for their continued commitment to a multi-agency approach to drug data. We also thank the health authorities in the North West Health Region for supporting this work and Jim McVeigh, Rachel Birtles and two anonymous referees for comments on the manuscript.
Conflicts of interest: none.