About the Epidemiology

Study Details

Public Health in British Columbia continues to receive reports of agranulocytosis related to levamisole in cocaine. Since the previous update August 12th, 2009 15 more cases have occurred. A standard case report form is used to collect case details and information is collated at the BC Centre for Disease Control. This form is available as a fillable PDF and can be accessed below, or by entering the address http://www.bccdc.ca/cocaine into your browser. Please continue to report new cases/episodes to your local public health.

We are performing a study to investigate the relationship of genetic markers to the development of agranulocytosis in relation to levamisole contaminated cocaine, and investigate the long term outcome of those affected by levamisole contaminated cocaine. Long term follow-up will facilitate the creation of better clinical management methods for these patients.

Background

Levamisole was previously used as an antihelmithic and colon cancer treatment, but has not been available in Canada since 2005. Levamisole is known to cause agranulocytosis in 3-10% of exposed persons. This reaction is thought to be associated with an autoimmune response and the HLA-B27 antigen.

Cases were identified in Alberta in November 2008 and subsequently in BC. An alert was sent out in BC on December 11th, 2008. To date 40 individuals with levamisole associated agranulocytosis have been reported in BC occurring between January 1st, 2008 and September 1st, 2010 (not including 2 recently reported, but for which we are lacking complete information). Some individuals have had repeat episodes of severe neutropenia - defined as neutrophil count < 0.5 per 109/L. There have been three reported deaths.

The US Dept Justice, DEA Cocaine Signature Program Report identifies the geographic origin of cocaine. During the 4th quarter 2008, 97% of cocaine tested in US was identified as originating from Columbia with an average purity of 78%. Levamisole has been identified in 20 to 47% of the cocaine bricks analysed.

Summary of BC cases

The following summarizes the details of the 40 individuals for whom report forms have been received. One case report from the interior of BC is pending.

• Sex: 24 (60%) female, 16 male
• Mean age: Females 37 yrs (range 22-52yr); Males 46.6yrs (range 27-64yr)Females significantly younger (p<0.5)
• Ethnicity: 23 First Nations, 1 Inuit; 6 Caucasian; 10 unknown
• Residence: please see map for places of residence. The breakdown of cases by the 5 health regions:

• Cocaine usage: all 40 cases use Cocaine (type of cocaine: 22 crack only; 1 crack and powder, 5 powder only; 12 unknown)
• Route use: 18 smoking; 2 smoking and snorting; 1 smoking and injection; 1 injection and snorting; 1 injection; 9 snorting; 8 unknown

Through laboratory data review Alberta has identified cases dating back to 2006.

Cases have also been reported in US (Vermont, New Mexico, Denver and Seattle). We are working closely with the other jurisdictions.

Figure 1. Residence of cases of agranulocytosis associated with cocaine Jan 2008-September 2010 (n=40)
 
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Figure 2. Number of episodes of agranulocytosis associated with cocaine (Jan 2008-September 2010; n=40)

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Figure 3. Symptom onset dates BC cases identified Jan 2008-September 2010; n=40.

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Clinical notes: Agranulocytosis associated with levamisole in cocaine
Suspect in persons with cocaine use and signs of infection- skin abscess, pneumonia, fevers etc which develop or progress rapidly
Diagnostic tests

• Urgent CBC and differential to identify neutropenia

Suggested management

• If neutrophil count is <1.0 and patient is febrile with an active infection, the patient will require urgent hospital admission and referral to haematologist.
• Perform infectious work-up including blood cultures; administer broad spectrum antibiotics (e.g. Piperacillin/Tazobactam, Imipenem or Ceftazidime)
• Filgastrim (G-CSF) should not be started until after consultation with haematologist

Recovery generally occurs in 7-10 days, but monitor closely. Recurrence is common and neutropenia may recur in about half of cases when re-exposed.