Case 1

A 13-year-old boy was admitted to a London hospital with a 4-day history of fever and headache. This acute admission was preceded by a 3-month history of gradual weight loss, dysuria and worsening testicular pain. There was a history of recent travel to Ethiopia, but the patient denied any history of consumption of unpasteurised foods, insect bites or unprotected sexual activity during his stay abroad. A Gram-negative coccobacillus was isolated from blood cultures after 48 h, and it was identified as Brucella melitensis. Although the blood culture bench was alerted to the possibility of the organism being Brucella spp within 24 h of the culture bottles flagging up positive, five staff members had directly manipulated the cultures on the open bench. It was not routine practice in this laboratory for positive blood cultures to be handled in a safety cabinet unless previously alerted to a risk. Subsequent enquiries revealed the patient had consumed camel milk during his stay abroad.

Case 2

A Caucasian man in his 20s was admitted to a second London hospital with an 8-week history of fever and fatigue. He denied any history of recent travel abroad, consumption of unpasteurised foods, insect bites or unprotected sexual activity. Four sets of blood cultures were taken, and a Gram-negative coccobacillus was isolated from all four aerobic bottles. At this stage brucellosis was suspected based on initial phenotypic characteristics. The isolate was sent to the Veterinary Laboratory Agency, Weybridge, Surrey, UK, where it was identified as B melitensis. Subsequent enquiries revealed the patient had travelled to the Algarve 9 weeks prior to hospital admission.

Case 3

A woman in her 20s from Northern Iraq was admitted to a third London hospital with a 4-week history of fever and joint pains. There was no history of insect bites, recent travel abroad or consumption of unpasteurised foods. An oxidase-positive Gram-negative coccobacillus was isolated from blood cultures after 48 h. The organism was not seen on initial Gram stain, but grew on cultures 48 h later. The isolate was identified as Brucella sp by the Veterinary Laboratory Agency. Subsequent enquiries revealed that 5 months previously the patient had consumed cheese that had originated from a small dairy farm in Iraq.

Case 4

A man in his 50s with a 3-week history of fever and low back pain was seen by his GP in London. There was no history of insect bites, consumption of unpasteurised food or unprotected sexual activity. The initial working diagnosis was suspected prostatitis. A Gram-negative coccobacillus was isolated from blood cultures taken at the GP practice. API20NE (bioMérieux, Marcy l’Etoile, France) gave a doubtful profile of Psychrobacter phenylpyruvicus. Brucella sp was not initially suspected by staff. 16S rDNA PCR was performed in-house, and this subsequently identified the organism as B melitensis. Subsequent enquiries revealed the patient had travelled to Egypt 6 weeks previously. On returning to London, he had been investigated extensively at a private clinic. The private laboratory had also isolated a Gram-negative coccobacillus, which again had given an API20NE profile of P phenylpyruvicus. Details of the numbers of staff members exposed, and postexposure follow-up procedures for the four cases, are summarised in table 1.

Discussion

Human brucellosis is now rare in the UK with fewer than 20 cases reported per year.1 Laboratory acquired brucellosis (LAB) is a concern as laboratory staff can fail to identify the organism due to unfamiliarity with the phenotypic characteristics of Brucella spp. Commercial biochemical identification kits such as API20NE can misidentify Brucella as Moraxella phenylpyruvica or P phenylpyruvicus.2

The risk of LAB is difficult to quantify because of a lack of systematic reporting, and has relied on case report publications and periodic laboratory surveys. A Spanish national survey of LAB demonstrated that risk was related to the number of isolates of Brucella spp handled per year, and most cases were related to non-compliance with biosafety measures.3 The attack rate of LAB has ranged from 30% to 100%. However the risk of transmission is not limited to staff who process the isolate.4

All exposed individuals in the report by Fiori et al were enrolled in a prospective study.5 Blood samples were collected weekly for the first 3 months following the accident, and then monthly for the following 12 months. The incubation period for LAB has been reported to be from 6 weeks to 5 months.6 7 Fiori et al. showed no correlation between incubation period and staff location in the laboratory when the incident occurred, with the exception of the person who was handling the specimen, who was the first to show signs of infection. This publication showed that seroconversion occurred before symptomatic illness in most cases, thus allowing early treatment. These reports highlight the importance of monitoring antibody titres in laboratory staff exposed to Brucella.

Robichaud et al reported LAB in one out of six laboratory staff who had directly manipulated the organism.8 Five laboratory staff who had received postexposure prophylaxis did not seroconvert or develop brucellosis. The laboratory staff member who developed brucellosis had declined prophylaxis, and symptoms preceded detection of seroconversion.

We outline the risk categorisation and postexposure management of laboratory staff in box 1. Several publications recommend serology, but in the UK there is no guidance, and the evidence suggests that serological follow-up may be needed.5 8 Box 2 describes interventions that may be helpful in preventing inadvertent exposure to brucella or other uncommon hazard group 3 pathogens.

Finally, we recommend that all Gram-negative coccobacilli from blood cultures and other sterile sites should be processed in appropriate facilities until hazard group 3 pathogens have been definitively excluded. This would be an important strategy in helping to reduce risk to laboratory staff.