BRIEF REPORT
METHODS
Anthrax Infection Among Heroin
Users in Scotland During 2009–
2010: A Case-Control Study by
Linkage to a National Drug
Treatment Database
Norah E. Palmateer,1 Colin N. Ramsay,2 Lynda Browning,3
David J. Goldberg,1 and Sharon J. Hutchinson1,4
1
Blood-Borne Viruses and Sexually Transmitted Infections, 2Environmental Public
Health, and 3Gastrointestinal Disease and Zoonoses, Health Protection Scotland,
and 4Department of Mathematics and Statistics, University of Strathclyde,
Glasgow, United Kingdom
Using a data-linkage approach, we conducted a case-control
study to investigate risk factors in an outbreak of anthrax
infection among Scottish heroin users. Factors associated
with an increased risk of infection included longer injecting
history, receiving opioid substitution therapy, and alcohol
consumption. Smoking heroin was associated with lower
risk of infection.
During December 2009–October 2010, 82 confirmed/probable
cases of infection with Bacillus anthracis (anthrax) were de-
tected across Scotland among drug using individuals [1, 2]. All
cases reported injecting and/or smoking heroin during the
week prior to onset of illness [2]. Most cases presented with
severe soft tissue infections, with the more seriously ill patients
having symptoms consistent with systemic infection. The pre-
sentations were generally not typical of classical cutaneous or
pulmonary anthrax [2]: a previously documented case in
Norway of anthrax in an injector [3] led the investigators to
propose the term “injectional” anthrax.
To determine the demographic/behavioral correlates of
anthrax infection, we conducted a case-control analysis of data
obtained via linkage of the Scottish anthrax cases to a national
drug treatment database.
Received 10 February 2012; accepted 14 May 2012; electronically published 22 May 2012.
Correspondence: Norah Palmateer, BScH, MSc, Meridian Court, 4th Fl, 5 Cadogan St,
Glasgow, G2 6QE, United Kingdom (norah.palmateer@nhs.net).
Clinical Infectious Diseases 2012;55(5):706–10
© The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail: journals.
permissions@oup.com.
DOI: 10.1093/cid/cis511
706 • CID 2012:55 (1 September) • BRIEF REPORT
The Scottish Drugs Misuse Database (SDMD) holds informa-
tion on individuals attending treatment services for problem
drug use (first visit or first visit in 6 months) [4], capturing
information from specialist drug services and general practi-
tioners across Scotland. Using data collated by Health Protec-
tion Scotland during the anthrax outbreak investigation, 82
confirmed/probable cases of anthrax were probabilistically
Downloaded from https://academic.oup.com/cid/article/55/5/706/351765 by guest on 30 March 2021
linked to the SDMD (data available to 31 March 2010) using
the limited identifiers available (first and fourth characters of
surname, first part postcode, sex, and date of birth). Data from
each linked case’s last SDMD registration were extracted. Ten
controls per linked case were randomly selected from the
SDMD and were matched to cases by attendance at the same
or nearby drug treatment service within a period of ± 12
months. Controls were restricted to individuals who had re-
ported using heroin in the month prior to registration.
Conditional (matched) logistic regression analyses were
conducted to examine the association between potential risk
factors, derived from the SDMD data, and case/control status.
Variables with P values <.1 (based on the univariable associa-
tion) were considered for inclusion in multivariable models.
Two multivariable models were fitted, examining the entire
sample and those who had reported ever injecting (according
to their SDMD registration).
Sensitivity analyses were conducted to examine the robust-
ness of the multivariable models to the exclusion of the fol-
lowing cases (and corresponding controls): 3 cases with
SDMD registration dates after anthrax onset, 14 cases with ≥5
years between registration and anthrax onset, and 9 cases who
had not reported taking heroin in the month prior to their
last registration. All analyses were undertaken in Stata version
9.2 software.
RESULTS
Sixty-five of 82 (79%) cases linked to the SDMD. A compari-
son of individuals who did and did not link to the SDMD
revealed that a significantly larger proportion of nonlinkers
lived in the west of Scotland (88% vs 62%, P = .03). Gender of
linkers and nonlinkers was identical (71% male). Linkers were
slightly older than nonlinkers (mean age 35.2 vs 32.6, median
age 36 vs 31, respectively), although this was not statistically
significant.
Table 1. Comparison of Demographic and Behavioral Characteristics Between Scottish Anthrax Cases (n = 65) and Controls (n = 650)

Unadjusted Conditional Logistic

Cases Controls Regression

Characteristic N % N % OR 95% CI P Value

Gender
Male 46 71 458 70 1.00
Female 19 29 192 30 0.98 .56–1.74 .96
Age at last attendance (years)
<25 12 18 147 23 1.00 … …
25–29 15 23 169 26 1.12 .50–2.53 .78
30–34 13 20 155 24 1.08 .47–2.50 .86
35+ 25 38 179 28 1.84 .85–3.98 .12
Time since onset of drug use (107
missing)

Downloaded from https://academic.oup.com/cid/article/55/5/706/351765 by guest on 30 March 2021

<9 years 11 21 154 28 1.00 … …
9–15 years 20 38 180 32 1.48 .67–3.26 .25
16+ years 21 40 222 40 1.17 .52–2.64 .70
Time since onset of problematic drug
use (82 missing)
<5 years 14 25 174 30 1.00 … …
5–9 years 11 20 187 32 0.71 .31–1.63 .42
10+ years 31 55 216 37 1.78 .88–3.61 .11
Ever injected (10 missing)
No 8 12 163 25 1.00 … …
Yes 57 88 477 75 2.67 1.21–5.87 .02
Injected in past month (72 missing)
No 21 36 257 44 1.00 … …
Yes 37 64 328 56 1.50 .83–2.71 .18
Time since onset of injecting, among
those who had ever injected (67
missing)
<5 years 18 35 174 41 1.00 … …
5–9 years 6 12 110 26 0.50 .19–1.33 .16
10+ years 27 53 142 33 2.00 1.00–3.97 .05
Shared needle/syringe in past month,a
among those who had injected in past
month (118 missing)
No 25 78 228 79 1.00 … …
Yes 7 22 59 21 1.36 .50–3.69 .55
Shared other injecting equipment in past
monthb, among those who had
injected in past month (142 missing)
No 22 69 175 67 1.00 … …
Yes 10 31 88 33 0.97 .41–2.27 .94
Route of heroin administration in past
monthc,d (4 missing)
Injecting, but not smokinge 28 50 242 37 1.00 … …
Injecting and smokinge 10 18 98 15 0.95 .43–2.12 .90
Smoking, but not injectinge 16 29 298 46 0.47 .24–.92 .03
Other only 2 4 8 1 2.64 .40–17.45 .32
Frequency of heroin taking in past
monthc (51 missing)
<daily 11 20 113 19 1.00 … …
≥daily 43 80 488 81 0.72 .34–1.50 .38

BRIEF REPORT • CID 2012:55 (1 September) • 707

Table 1 continued.

Unadjusted Conditional Logistic

Cases Controls Regression

Characteristic N % N % OR 95% CI P Value

Heroin quantity in a typical day during
past monthc (450 missing)
<0.5 g 10 53 107 45 1.00
≥0.5 g 9 47 130 55 0.77 .29–2.02 .60
Currently receiving any prescription
drugsf (149 missing)
Any OST ± other drug 25 48 153 30 1.00 … …
Other drug only 1 2 48 9 0.09 .01–.79 .03
None 26 50 313 61 0.41 .21–.79 .01
Ever tested for hepatitis C (288 missing)

Downloaded from https://academic.oup.com/cid/article/55/5/706/351765 by guest on 30 March 2021

No 13 31 159 41 1.00 … …
Yes 29 69 226 59 1.53 .77–3.05 .22
Any alcohol consumption in past month
(234 missing)
No 24 55 300 69 1.00 … …
Yes 20 45 137 31 1.88 .98–3.62 .06
Excessive alcohol consumption in past
monthg (275 missing)
No 28 82 355 87 1.00 … …
Yes 6 18 51 13 1.61 .61–4.20 .34

Abbreviations: CI, confidence interval; OR, odds ratio; OST, opioid substitution therapy.
a
Sharing may include borrowing or lending used needles/syringes.
b
Other equipment includes spoons, filters, or water.
c
Among those who reported taking heroin in the last month (56 of 65 cases, and all controls).
d
Injecting includes intravenous or intramuscular injecting; smoking includes snorting and inhalation; “other” includes routes of administration reported as
swallowing, oral, or other.
e
These categories may also include those who take heroin via the “other” route, as defined above.
f
Other drug refers to any prescription drug other than opioid substitutes (eg, antidepressants, sedatives, etc).
g
Excessive defined as >14 units/week for women and >21 units/week for men.

Table 1 presents the unadjusted analyses of demographic/
behavioral characteristics of cases and controls. Ever injecting,
time since onset of injecting, route of heroin administration,
receiving opioid substitution therapy (OST), and alcohol con-
sumption were significantly associated with case/control
status.
In adjusted analyses, among all subjects, those who had
been injecting for ≥10 years (adjusted odds ratio [AOR], 2.43;
95% confidence interval [CI], 1.31–4.52) and those who were
currently receiving OST (AOR, 2.74; 95% CI, 1.40–5.37) were
both more likely to be a case (Table 2). Individuals who only
smoked heroin in the past month were less likely to be a case
(AOR, 0.42; 95% CI, .20–.86). Alcohol consumption in the
past month was marginally associated (P = .09) with greater
odds of being a case (AOR, 1.77; 95% CI, .91–3.47). When
analyses were restricted to those who had ever injected
(Table 2), the effect sizes and P values were similar to those
generated using the whole sample, with the exception of
smoking heroin, which was no longer significantly associated
with case status (AOR, 0.57; 95% CI, .28–1.15, P = .12).
The models generated from sensitivity analyses were very
similar to that generated using all cases (not shown; available
from authors on request).
DISCUSSION
By using a record-linkage approach to generate case-control
data [5], we have identified selected risk factors for anthrax
infection in the recent Scottish outbreak. This approach was
used because it was not possible to undertake a traditional
case-control study due to logistic constraints, and because the
information collected during the anthrax outbreak investiga-
tion did not have controls for comparison. We found that
longer injecting history, receiving OST, and alcohol

708 • CID 2012:55 (1 September) • BRIEF REPORT

Table 2. Multivariable Conditional (Matched) Logistic Regression Analyses on (a) All Anthrax Cases and Controls, and (b) Anthrax
Cases and Controls Who Reported Having Ever Injected Drugs on Their Last Scottish Drugs Misuse Database Registration

b) Subjects Who Reported Ever Injecting Drugs

a) All Subjects (N = 715) (N = 488)

Adjusted Conditional Adjusted Conditional

Cases Controls Logistic Model Cases Controls Logistic Model

Characteristic N % N % AOR 95% CI P Value N % N % AOR 95% CI P Value

Time since onset of injecting
<10 years 24 37 284 44 1.00 … … 24 42 257 60 1.00 … …
10+ years 27 42 142 22 2.43 1.31–4.52 <.01 27 47 128 30 2.49 1.33–4.67 <.01
Never injected 8 12 163 25 1.02 .37–2.83 .96 … … … … … … …
Missing 6 9 61 9 1.08 .38–3.03 .89 6 11 46 11 1.13 .39–3.32 .82
Route of heroin administration—

Downloaded from https://academic.oup.com/cid/article/55/5/706/351765 by guest on 30 March 2021

only smoked heroin in past
montha
No 49 75 352 54 1.00 … … 45 79 300 70 1.00 … …
Yes 16 25 298 46 0.42 .20–.86 .02 12 21 131 30 0.57 .28–1.15 .12
Currently receiving OST
No 27 42 361 56 1.00 … … 24 42 239 56 1.00 … …
Yes 25 38 153 24 2.74 1.40–5.37 <.01 23 40 118 27 2.44 1.16–5.14 .02
Missing 13 20 136 21 1.42 .60–3.35 .42 10 18 74 17 1.56 .63–3.91 .34
Any alcohol consumption in past
month
No 24 37 300 46 1.00 … … 20 35 207 48 1.00 … …
Yes 20 31 137 21 1.77 .91–3.47 .09 19 33 103 24 1.89 .92–3.86 .08
Missing 21 32 213 33 0.98 .29–3.25 .97 18 32 121 28 1.58 .33–7.61 .57

Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; OST, opioid substitution therapy.
a
In model a), the “No” category includes 4 controls with missing route of heroin administration and 9 cases who did not report taking heroin (consisting of 2
cases who reported taking other illicit drugs, 6 cases who reported taking no illicit drugs, and 1 case missing this information); in model b), it includes 6 cases
who did not report taking heroin (consisting of 1 case who reported taking other illicit drugs, 4 cases who reported taking no illicit drugs, and 1 case missing this
information).

consumption were positively associated with anthrax infection.
We also found that only smoking heroin was associated with
lower risk of infection. The risk factors identified in this study
are consistent with the hypotheses developed, but not formally
confirmed, in the investigation of the anthrax outbreak [2].
Notably, we did not find an association between sharing in-
jecting equipment and anthrax infection. This is consistent
with other evidence, described in the outbreak report [2],
which strongly points to the heroin itself as the source of in-
fection. The latter is also supported by the observed correla-
tion between length of injecting and infection: whereas we
might have expected younger, less experienced drug users—
who tend to engage in riskier behavior [6]—to have a greater
burden of infection, the opposite was observed. Older age/
longer injecting career have previously been implicated in bac-
terial soft tissue infections among injectors, which may have
been explained by the higher propensity for older individuals
to inject into the skin/muscle—an anaerobic environment in
which Clostridia species proliferate [7, 8]. Since B. anthracis is
aerobic, this is perhaps less likely to be the case here. The as-
sociation between anthrax and longer injecting career may
reflect the poorer health and therefore greater susceptibility to
infection of long-term drug users [9, 10]. Similarly, the associ-
ation between alcohol and anthrax may reflect higher sus-
ceptibility to infection due to alcohol’s immunosuppressive
effects [11].
With regard to route of heroin administration and risk of
infection, it is conceivable that the intravenous administration
of heroin is more conducive to the germination of spores and
proliferation of vegetative organisms than smoking/inhaling
heroin. However, inhalation of anthrax spores via heroin inha-
lation/smoking is a biologically plausible route of infection,
and evidence from the outbreak case histories verified that in-
fection did occur in noninjecting heroin users, including at
least 1 fatal case.
The finding that those who were currently receiving OST
were more likely to have had anthrax was significant, even
after adjustment for time since onset of injecting.

BRIEF REPORT • CID 2012:55 (1 September) • 709

Nevertheless, there may still be residual confounding and this
association may simply reflect the more problematic and long-
standing drug use of the anthrax cases, since the likelihood of
being in treatment for drug use increases with increasing
length and severity of drug use.
This study has a number of limitations. First, because the
linked data was from a preexisting source (ie, it was not col-
lected with the specific purpose of investigating the anthrax
outbreak), we were limited to examining the data that are col-
lected for drug misuse treatment.
Second, there was a long time delay between SDMD regis-
tration and anthrax onset for many of the cases. Thus, the be-
havior that was recorded during an individual’s historical
attendance at a treatment facility may not be representative of
his/her behavior in the period immediately preceding onset of
anthrax illness. Nevertheless, studies have demonstrated that
drug-taking behavior can be consistent over time, particularly
among long-term heroin users [10], who are highly represent-
ed among our linked anthrax cases.
Third, there was a large amount of missing data in the drug
treatment records; thus, the current study was likely under-
powered to detect some associations.
Fourth, 17 anthrax cases did not link to the SDMD. Plausi-
ble reasons for this could include: incomplete coverage of
drug treatment services by the SDMD, that the cases had
never received treatment for drug misuse, or that there were
inaccuracies in the identifying information used for record
linkage. The predominance of nonlinkers from the west of
Scotland, and Glasgow in particular (9 of the nonlinkers),
likely reflects an issue with completeness of reporting of data
to the SDMD in this area since mid-2009 due to the introduc-
tion of an electronic system (Andrew Deas, Information Ser-
vices Division, personal communication, 2012). To verify if
the exclusion of these cases would bias our findings, we com-
pared data on injecting/smoking heroin in the week prior to
anthrax onset and found no statistically significant difference
between the linkers and nonlinkers (5% of linkers vs 0% of
nonlinkers had only smoked heroin, P = .64).
In conclusion, we have demonstrated a method of using
routinely collected data to enable a case-control analysis where
otherwise this would not be possible, which can be used to
support hypotheses and/or corroborate the findings of other
investigations (eg, epidemiological, clinical, microbiological, or
710 • CID 2012:55 (1 September) • BRIEF REPORT
criminal justice). Understanding the risk factors for anthrax
infection may help to inform risk communication in future
outbreaks of anthrax or other bacterial infections affecting
drug users.
Notes
Acknowledgments. We would like to thank Catherine Taylor from In-
formation Services Division of National Services Scotland for undertaking
the data linkage and Amanda Weir from Health Protection Scotland for
her assistance with the random selection of controls.
Financial support. This work was supported by Health Protection
Scotland. No direct funding was received for the study.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
Downloaded from https://academic.oup.com/cid/article/55/5/706/351765 by guest on 30 March 2021
References
1. Ramsay CN, Stirling A, Smith J, et al. An outbreak of infection with
Bacillus anthracis in injecting drug users in Scotland. Euro Surveill
2010; 15:pii=19465.
2. National Anthrax Outbreak Control Team. An outbreak of anthrax
among drug users in Scotland, December 2009 to December 2010.
Available at: http://www.documents.hps.scot.nhs.uk/giz/anthrax-outbreak/
anthrax-outbreak-report-2011-12.pdf. Accessed 28 December 2011.
3. Ringertz SH, Hoiby EA, Jensenius M, et al. Injectional anthrax in a
heroin skin-popper. Lancet 2000; 356:1574–5.
4. Information Services Division (ISD) Scotland. Drug Misuse Statistics
Scotland 2010. Available at: http://www.drugmisuse.isdscotland.org/
publications/10dmss/10dmss.pdf. Accessed 28 December 2011.
5. Bellis MA, Beynon C, Millar T, et al. Unexplained illness and deaths
among injecting drug users in England: a case control study using Re-
gional Drug Misuse Databases. J Epidemiol Commun H 2001;
55:843–4.
6. Garfein RS, Doherty MC, Monterroso ER, et al. Prevalence and inci-
dence of hepatitis C virus infection among young adult injection drug
users. J Acq Immune Defic Syndr Hum Retrovirol 1998; 18(suppl 1):
S11–9.
7. Hankins C, Palmer D, Singh R. Unintended subcutaneous and intra-
muscular injection by drug users. CMAJ 2000; 163:1425–6.
8. Brett MM, Hood J, Brazier JS, Duerden BI, Hahné SJ. Soft tissue in-
fections caused by spore-forming bacteria in injecting drug users in
the United Kingdom. Epidemiol Infect 2005; 133:575–82.
9. Rosen D, Hunsaker A, Albert SM, Cornelius JR, Reynolds CF 3rd.
Characteristics and consequences of heroin use among older adults in
the USA: a review of the literature, treatment implications, and recom-
mendations for further research. Addict Behav 2011; 36:279–85.
10. Darke S, Mills KL, Ross J, Williamson A, Havard A, Teesson M. The
ageing heroin user: career length, clinical profile and outcomes across
36 months. Drug Alcohol Rev 2009; 28:243–9.
11. Szabo G. Alcohol’s contribution to compromised immunity. Alcohol
Health Res World 1997; 21:30–41.