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Published Date: 2012-06-29 19:59:24
Subject: PRO/AH/EDR> Anthrax - Germany (04): formal report
Archive Number: 20120629.1185257

ANTHRAX - GERMANY (04): FORMAL REPORT
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Date: 28 Jun 2012
Source: Eurosurveillance [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20204

Fatal anthrax infection in a heroin user from southern Germany
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TT Holzman (Institute of Medical Microbiology and Hygiene, University Hospital of Regensburg, Regensburg, Germany) et al., Eurosurveillance, Volume 17, Issue 26, 28 June 2012 Rapid communications

Abstract: Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of _Bacillus anthracis_. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.

In early June 2012, a case of anthrax infection was identified in an injecting drug user in Germany. Anthrax wasn't suspected initially and the patient died on the day of hospital admission. 2 days later anthrax was confirmed and the relevant authorities were informed. This report underlines the importance of considering anthrax as a possible diagnosis in injecting heroin users presenting with fever or sepsis at emergency rooms and of the rapid management of such cases.

Clinical case description:
In early June 2012 an injecting drug user in their 50s presented at the emergency department of a hospital in the south of Germany, with a 2-day history of worsening swelling and reddening at an injection site, nausea and dyspnoea. The patient had been on oral substitution therapy for 2 years. Moreover, a history of chronic hepatitis C infection with liver cirrhosis was reported. In the next hours after admission to hospital, the patient developed respiratory failure and was transferred to the intensive care unit (ICU) where he was ventilated mechanically. An elevated white blood cell count (15.9 cells/nL), anaemia (haemoglobin 10.4 g/dL), thrombocytopenia (38 cells/nL), elevated procalcitonin (1.05 ng/mL) and hypokalaemia (2.5 mmol/L) were observed. Elevated liver enzymes, lowered coagulation parameters and extremely high levels of D-dimers (>36,364 ng/mL) were pointing to multi-organ failure. Blood and urine cultures were sent to the Institute of Medical Microbiology and Hygiene, University of Regensburg. The patient's condition worsened and he died on the day of admission due to a septic shock with multi-organ failure and massive disseminated bleeding. At the time, there was no clinical suspicion of anthrax.

Control measures:
The District Health Office was informed about the suspected case of human _B. anthracis_ infection immediately after obtaining the PCR results. Their experts got involved in the management of the case in close contact with the diagnostic institutions, the police authorities and the Task Force Infectiology of the Bavarian Health and Food Safety Authority (LGL). Health officials considered contaminated heroin or cutting agents mixed with the heroin as possible source of the infection. Further investigations by the German police authorities were initiated immediately.

The competent public health authorities at national level were informed immediately about the confirmation of _B. anthracis_. The information on the occurrence of the case was distributed to the public health authorities in all 16 German federal states, at international level through the Early Warning and Response System (EWRS) of the European Commission and via ProMED-mail and according to the International Health Regulations (IHR). In Bavaria, the medical associations were informed. Substance abuse counselling agencies were contacted nationally and at European level through the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in order to spread the information among drug users. Additional information and materials were published by the public health institutes on their websites. The 1st results of molecular genotyping of the strain showed close relationship to strains from a large anthrax outbreak among IDUs in Scotland.

Identification of the 2nd case:
Then, 2 weeks after the 1st case was admitted to hospital, a 2nd case of anthrax was identified in an IDU from the same region as the 1st case. The patient is stable under antibiotic therapy after surgical debridement. The raised level of awareness created with the 1st case lead to a much faster workflow in the laboratory analysis in the 2nd case. _B. anthracis_ was confirmed 3 hours after blood cultures turned positive.

Discussion:
Injectional anthrax has 1st been reported 1988 as 4th route of infection besides cutaneous, gastrointestinal and inhalational anthrax infections. The 1st anthrax case related to injecting drug use was described 2000 from Norway. There were no subsequent reports of injectional anthrax until 10 Dec 2009 when anthrax was identified in blood cultures from two injecting drug users from Glasgow, Scotland. In the following months an increasing number of cases were identified. By the end of the outbreak in December 2010, there were 47 confirmed cases of injectional anthrax (including 13 deaths), 35 probable cases (including one death) and 37 possible cases in Scotland and 5 cases including 4 deaths in England. There were 2 confirmed cases in Germany related to this outbreak, including one fatal case. The favoured outbreak hypothesis assumed that heroin had been in contact with goat skin contaminated with anthrax spores during transportation to Scotland. Risk factors for infection were longer injection history, receiving opioid substitution therapy, and alcohol consumption. All cases of injectional anthrax reported so far including the case presented here were not associated with the typical black eschar seen in patients with cutaneous anthrax.

Because _B. anthracis_ is seen very rarely in Germany and other developed countries, laboratory staff and clinicians should raise their attention when Gram-positive bacilli growing in chains are detected in clinical specimens.

_B. anthracis_ cannot be reliably distinguished from _B. cereus_ by growth characteristics, bacterial cell morphology or biochemical methods. The applicability of MALDI-TOF-MS for the identification of _B. anthracis_ was demonstrated elsewhere. Because of safety regulations, _B. anthracis_ and other potential bioterroristic agents are not included in the manufacturer's (Bruker Daltonics) database. As in our case, the isolate is classified as _B. cereus_ with the standard databases. Using a special database, containing the missing spectra, _B. anthracis_ is identified correctly. The manufacturer discourages the standard use of the B. anthracis spectra due to misidentification of members of the _B. cereus_ group. Consequently, the result 'B. cereus' in combination with a patient's history of injecting drug use should lead to further diagnostic steps. To differentiate between _B. anthracis_ and non-anthracis Bacillus species harbouring anthrax-specific virulence plasmids, PCR targeting a chromosomal marker should be performed in addition to PCR assays covering the virulence plasmids pXO1 and pXO2. Non-pathogenic _B. anthracis_ strains not containing plasmids can be identified using this combination as well.

Conclusions:
Health professionals and diagnostic laboratories should consider anthrax as a possible diagnosis in injecting heroin users presenting with fever or sepsis at the emergency room. The observed re-emergence of drug-related anthrax in Germany supports the hypothesis that heroin may provide a continuing entry route of _B. anthracis_ into western Europe.

Recommendations and Lessons Learnt:
1: When growth of Bacillus cereus sensu lato is identified by the MALDI species typing database, a sound anamnesis of the underlying clinical case should be performed.
2: Suspicious cultures should be transferred to a biosafety level 3 environment and, whenever possible, a spectrum of validated molecular tests should be kept in stock for level 3 pathogens (especially _B. anthracis_).
3: An agreed case definition and protocol for alerting the authorities should be available and known to all microbiologists and clinicians.
4: Appropriate reporting channels should be maintained and exercised by the public health authorities to prevent that similar (or parallel) cases remain undetected.
5: Confirmatory PCR testing in a specialised laboratory should be immediately requested. Diagnostic laboratories should know such specialised laboratories in their vicinity for support and check the logistics of sample transport in a situation of emergency (ideally before they encounter their 1st uncommon strain).
6: Clinicians and microbiologists should be trained on a regular basis in the identification of _B. anthracis_ and other rare infectious diseases that are highly pathogenic.

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[Because of space limitations only parts of this valuable paper are posted. Members are encouraged to go to the full text for details.

According to my notes, anthrax is sporadic in German livestock. The latest were 2 outbreaks in Bayern with 4 affected cattle; a dead deer had been noted one week earlier. 2 years before dirt had been dumped in the field where the animal cases occurred from an excavation site for a new building. Previously there had been a bovine case in 2000 and outbreaks in 1994 and 1992. There had been human cases in 1992 (2), 1993 (1) and 1994 (1) and the heroin associated death in 2009.

Intrinsically there is nothing complicated about recognising _B. anthracis_ either in stained blood smears or on culture on sheep blood agar. It is really quite easy. But if those skills are not maintained, we depend more and more on ever more advanced technology and expense. Logically the German medical and public health groups would be wise to maintain professional contacts and interactions with their veterinary colleagues.

It has been brought to my attention that during the events in Scotland in 2009/2010 the police were actively collecting heroin off the street so it could be tested and analysed. Unfortunately no positive samples were found. The German authorities might be luckier. The Scottish experience indicated that the contamination was very unevenly distributed -- a shared batch drawn up in the same syringe from the same spoonful would kill one but other would be totally unaffected. Also the necessary injection dose is very small; one can kill goats when injecting with around 125-150 spores and all we are considering is infecting humans. Because heroin addicts delay getting medical attention, many die. - Mod.MHJ

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1zJl.]

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