Public Health in British Columbia continues to receive reports of agranulocytosis related to levamisole in cocaine. Since the previous update April 15th there have been 6 further cases. A standard case report form is used to collect case details and information is collated at the BC Centre for Disease Control. Please continue to report new cases/episodes to your local public health.

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 associated with an autoimmune response and HLA-B27 antigen.

Cases were identified in Alberta in November 2008 and susequently in BC. An alert was sent out in BC on December 11th, 2008. To date 27 individuals with levamisole associated agranulocytosis have been reported in BC occurring between January 1st, 2008 and August 9th, 2009. Some individuals have had repeat episodes of severe neutropenia - defined as neutrophil count < 0.5 per 109/L.

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 25 individuals for whom report forms have been received. Two case reports from Vancouver Island in 2008 are pending and information included in the map only.

• Sex: 17 (68%) female, 8 male
• Mean age: Females 35 yrs (range 22-51yr); Males 46yrs (range 32-63yr)
  Females significantly younger (p<0.5)
• Ethnicity: 16 First Nations, 1 Inuit; 4 Caucasian; 4 unknown
• Residence: 6 cases Chiliwack, 4 Port Hardy, 4 Prince George; 5 Victoria
  Only 2 cases in Vancouver - see map Figure 1.
  Repeat episodes: 13 cases have had one episode only - see Figure 2.
  Date of symptom onset is shown in Figure 3.
• Cocaine used: 15 crack only; 1 crack and powder, 3 powder only; 6 unknown
• Route use: 12 smoking; 2 smoking and snorting; 7 snorting;
  3 unknown 1 injecting

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-April 2009 (n=27; includes 2 earlier Victoria cases)

Figure 2. Number of episodes of agranulocytosis associated with cocaine (Jan 2008-April 2009; n=25)

Figure 3. Symptom onset dates BC cases identified Jan 2008- Aug 2009 n=25

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
• Urine collected within 48 hours of last cocaine use can be tested for levamisole
• Please contact your local Medical Health Officer (MHO) for more details

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.