international meeting on clostridium novyi and co. … meeting on clostridium novyi and co. the drug...

International meeting on Clostridium novyi and Co.

The drug injector outbreaks.

The outbreak in England

Dr Jane Jones, Specialist Registrar, PHLS,CDSC

On behalf of the PHLS, CDSC/CPHL outbreak investigation team;

• Tamara Djuretic and Jane Jones (Specialist Registrars, Public Health)

• Noel Gill (Consultant Epidemiologist)• Gordon Nichols (Principal Scientist)• Vivian Hope (Senior Scientist)• Andrew Weild (Scientist)• Robert George (Consultant Microbiologist)• Jane Salmon (Specialist Registrar,

Microbiology)

Aspects to be covered

• Response to the outbreak• Epidemiology and clinical features• Some recommendations arising

• …..Not microbiological aspects

Recognition of the problem

• PHLS, CDSC formally informed of a cluster of cases of unusual illness in injecting drug users in Glasgow on 10th May

• No similar cases had been notified in England/Wales at this time

• A case of wound botulism in an injecting drug user in London (with Scottish links) was notified to CDSC on 13th May

Active case finding

• 18th May 2000 - electronic message sent to CsCDCin England and Wales to;– alert them to the problem– ask them to contact all intensive care and

infectious disease units to actively seek cases• 19th May; International rapid alert issued by the

Department of Health in the UK• Two further electronic messages sent to CsCDC on

23rd and 30th of May; requesting nil returns

Case definition used for case finding

“ Any drug user who injected intramuscularly or subcutaneously and had a severe systemic inflammatory reaction requiring intensive or high dependency treatment from April 1st 2000”

Definitions used for epidemiological investigation (1)

Possible• a drug injector who presented to

hospital with an abscess or other significant inflammation at an injection site

Definitions used for epidemiological investigation (2)

Probable• a drug injector who presented to hospital with

an abscess or other significant inflammation at an injection site, and had either– a severe inflammatory process (large abscess/extensive

oedema) at or around this site, or – a severe systemic inflammatory reaction with evidence of

multi-organ failure and a high white cell count

Definitions used for epidemiological investigation (3)

Definite• a drug injector who presented to hospital with

an abscess or other significant inflammation at an injection site, and had both;– a severe inflammatory process (large abscess/extensive

oedema) at or around this site, and– a severe systemic inflammatory reaction with evidence of

multi-organ failure and a high white cell count

Definition used for focussing microbiological investigation

Definite syndromic• a drug injector admitted to hospital or found dead

since April 1st 2000 with soft tissue inflammation (i.e. abscess, cellulitis, fasciitis, or myositis) at an injection site, and either;– severe systemic toxicity (i.e. sustained systolic blood

pressure <90mmHg despite fluid resuscitation and total peripheral white cell count >30,000/mm3), or

– postmortem evidence of a diffuse toxic or infectious process including pleural effusions and soft tissue oedema or necrosis

Information collection and collation

• Reports of cases received by designated personnel at CDSC• Database maintained of all reports with classification of each

case as “possible”, “probable” or “definite”• Minimum dataset collected for all cases• More detailed data collection on “definite”/”probable” cases

using standard proforma (completed by CCDC/microbiologist/clinician)

• Detailed medical record examination for cases meeting “definite”/”probable” case definition and resident in North WestEngland (n=11) (performed by SpRs Public Health, CDSC)

Epidemiology (1)Time• April 1st - August 31st 2000; In England and Wales, 45 cases of

drug injectors with injection site soft tissue inflammation resulting in hospitalisation or death were notified to CDSC.

• First case admitted 8th April, last on 4th July. Of these;– 15 definite cases– 11 probable cases– 3 possible cases– 16 excluded

• NB/ Four definite cases were subsequently identified which had occurred before April 1st. These occurred in February and March.

Epidemic curve Severe illness in injecting drug users in England and Wales 2000

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

03/04 - 09/0410/04 - 16/0417/04 - 23/0424/04 - 30/0401/05 - 07/058/05 - 14/0515/05 - 21/0522/05 - 28/0529/05 - 04/0605/06 - 11/0612/06 - 18/0619/06 - 25/0626/06 - 02/0703/07 - 09/0710/07- 16/0717/07 - 23/0724/07 - 30/07

Date of hospital admission

Num

ber o

f cas

es

Definite casesProbable cases

Epidemiology (2)

Place

• Of the 26 cases identified as “definite”/ “probable”, 17 were resident in the North of England

Epidemiology (3)

Person

Of the 26 “definite”/ “probable” cases;– 13 (50%) male– Median age 32 years (range 23-48)– 15 (57%) intramuscular/subcutaneous

injectors

Clinical course

• Injection site inflammation, often very painful; abscess like (but with no pus)/gross oedema/extensive cellulitis/bruising.

• Median of three days between onset of symptoms and hospitalisation (range 0-20 days)

• Sudden deterioration; hypotension, shock, hypothermia, respiratory failure

• Case fatality rate 50% (13/26) overall for “definite”/ “probable” cases; 80% for “definite” cases and 9% for “probable” cases

• Median time from date of onset to death 4 days (range 1-20 days)

Investigations (not including microbiology)

• Peripheral white cell count available for 21 of the 26 “probable”/ “definite” cases;– “definite” median = 51,900 cells/mm3

– “probable” median = 15,000 cells/mm3

– overall median = 39,000 cells/mm3 (range 5,000 to 115,000 cells/mm3 )

• Where information available about hepatitis serology (n=12); three Hepatitis B positive, five Hepatitis C positive

• Other common features; high haemoglobin, deranged clotting, raised creatine kinase, ST changes on ECG, pulmonary oedema on CXR

• Pleural effusions commonly noted at post mortem

Postmortem toxicology. A potential source of bias in attribution of cause

of death in drug injectors ?

• Antemortem features and postmortem results examined for fifteen “definite”/ “probable” cases who died...– Where toxicology results not available to pathologist at PM

(n=11), death was attributed to;• “acute infectious process” - Nine • “unascertained” - Two

– Where toxicology results available to pathologist at PM (n=4), death was attributed to;

• “acute infectious process” - One • “overdose” - Three

– levels of questionable significance– one case with likely causative organism identified

Public health action taken

• Development of microbiological investigation protocol for clinicians, pathologists and microbiologists

• Development of advice to doctors re the clinical management of cases

• Development of advice to drug injectors• Updated information pack to all CsCDC in England

and Wales for ongoing surveillance

Lessons learned

• Active surveillance nationwide depended crucially on the participation of local CsCDC, microbiologists and clinicians

• Close interagency working essential; particular issues about theoverlap between public health priorities and legal requirements

• Importance of development of standard data collection and microbiological investigation protocols

• Mechanisms for timely data sharing essential for outbreaks crossing national borders

• Timely communication to clinicians and the affected population considered to be essential public health actions

Implications for public health

• Heroin addicts have 12 times the mortality risk of the rest of the population

• Devising an appropriate public health response to this problem requires information on causes of death as well as numbers.

• More research is required into the range of infections, common and unusual, which occur in drug injectors

• Routine toxicological investigation might bias attribution of cause of death towards overdose and away from other causes e.g. acute infections.

• Deaths in drug injectors should be more thoroughly investigated.

Recommendations (1)

• Clinicians treating drug injectors should maintain a high index of suspicion about “unusual” presentations, seek advice about microbiological investigation, and be prepared to inform their local public health department promptly should they see a cluster of such cases

• Agencies in contact with drug injectors should continue to educate them about the need to seek prompt healthcare for unusual skin infections/inflammations

• Research is required into the range of microbes which may occur in heroin and the circumstances in which these may become pathological

Recommendations (2)

• National and European systems for surveillance of severe illness (particularly infections) should be considered, since early warnings of potential problems might avert preventable morbidity and mortality through appropriate advice to cliniciansand users.

• Systems for rapid national and international communication and database maintenance should be consolidated and formalised

• Law enforcement agencies and public health authorities should work together to ensure that public health investigation priorities and legal requirements can be satisfactorily reconciled in the event of future similar incidents