Report into the investigation of ESR meningitis infection case of Dr Jeannette Adu-Bobie
Author: Dr Geraint Emrys, Department of Labour Chief Adviser Occupational Health
Date: 30 July 2008
To advise you of the result of my enquiries and review of the previous investigations into the reported case of suspected laboratory-acquired infection at the ESR Kenepuru site.
In March 2005, a visiting specialist, Dr Jeannette Adu-Bobie contracted meningococcal disease while working at the ESR Laboratory Kenepuru, in Porirua.
Dr Adu-Bobie has a PhD in microbiology obtained from Imperial College in London, and was employed by Chiron Vaccines (USA). She came to New Zealand as an expert in her field to specifically study meningococcal disease and the work of ESR in the Meningococcal Vaccine Antibody Testing Laboratory (MVATL).
Dr Adu-Bobie had been in New Zealand only 20 days, and at ESR for only 7 working days, at the time she contracted meningococcal septicaemia. She was critically ill and suffered terrible injuries as a consequence of this infection as she required amputation of her legs, left arm and digits of her right hand.
Dr Adu-Bobie had completed standard laboratory training and induction in the Meningococcal Vaccine Antibody Testing Laboratory (MVATL). She had performed tasks in the laboratory for only a few days before becoming ill.
Three investigations were undertaken at that time. These included:
- an internal investigation by ESR
- an independent external expert investigation requested by ESR, and
- the Department of Labour investigation
The conclusions of the three reports were consistent in that they did not identify any direct link as to the cause (mechanism) of this infection in relation to activities occurring at the ESR laboratory. The findings noted that:
- ESR met the appropriate standards of containment for dangerous pathogens
- ESR had no failure or deficiencies of their Standard Operational Procedures (SOPs)
- ESR had taken all practicable steps to manage the safety of staff
- ESR had adequate staff training in the form of induction and ongoing supervision, and
- the organism that infected Dr Adu-Bobie was found to be indistinguishable from that under study at the laboratory and prevalent in the community
The original investigation by the Department identified no breach of the Health and Safety in Employment Act 1992, and found no grounds to consider enforcement action against any parties. The investigation concluded “…there is no clear evidence to identify the source of the infection, and as such, no inference can be made as to the cause of the exposure.” The Department subsequently said it was extremely unlikely that Dr Adu-Bobie contracted this disease while at ESR.
In February 2006, Dr Adu-Bobie presented a journal article to DoL that suggests laboratory workers have a higher risk of infection. In response the Service Manager at the time agreed to look into this further.
The progress of this work has been slower than hoped for a number of reasons including change of staff, widening scope of the review, consulting with experts and responding to issues raised when communicating with Dr Adu-Bobie. In response to the staff changes, Dr Geraint Emrys, Chief Adviser, Occupational Health was instructed by the Group Manager Workplace Services of the Department of Labour to take ownership of this work and see it through to conclusion.
The new Regional Manager for the central region, Mike Munnelly, instructed that this work not only reviews the investigation details but also the conclusion drawn about the likely source of the infection.
A decision was made to split the work into two parts. The first and main part was the completion of a report into the standards associated with handling dangerous pathogens in a laboratory. The second piece of work was to review the original investigation, make further enquires as necessary and report back.
In December 2007 the Department released the report Review of Laboratory Practices in Handling Neisseria meningitidis. This review concluded that the standards recognised in New Zealand laboratories were consistent with international recommendations. The report concluded that there is no clear or urgent need to change laboratory safety standards.
The review noted that a number of potentially laboratory-acquired infections had been investigated world wide. The level of containment of Neisseria meningitidis was appropriate at level 2 (out of four levels). A higher level of containment is recommended for other organisms. Handling this organism represents a significant hazard, but all practicable steps would be achieved if Level 2 control measures were in place. Under these conditions the residual risk is considered acceptable. Universal measures, good laboratory practices, basic skills, training and experience and SOPs all form part of the control measures to reduce the risk associated with this hazard.
The review of laboratory practices report did not examine the details of this particular case. It dealt strictly with the article Dr Adu-Bobie presented and its implications for safety standards in New Zealand.
During the period that the review was being developed there was regular communication with Dr Adu-Bobie and significant effort was made to confirm the details of any declaration and the likely significance of these.
A review of the case has been undertaken. This has included:
- reviewing all the information gathered for the original investigation
- visiting ESR Kenepuru on three occasions to seek further information, clarification of potentially new information and seek comment on significance
- multiple e-mail communications, phone conversation and a face-to-face meeting (in London) with Dr Adu-Bobie
Inquires were made into a number of technical issues including, lifting of plates, condensation in the plates, wiping of condensation from plate lids, plating on the bench, plating from frozen or solid, the part played of individual actions and standard operating procedures.
Dr Adu-Bobie declared when initially questioned after becoming ill that she had wiped condensate from the plate lids. ESR had not previously been aware of this and no witnesses have come forward who were aware of this. It was, however, accepted that Dr Adu-Bobie did perform this activity. This activity was outside of the SOPs and should therefore not have been performed. SOPs are directive, “you shall”, indicating only the actions that should be taken. They do not indicate the things you do not do as these are covered in normal laboratory practice and behaviours. The scientific advice obtained was that this action should not have increased the risk of infection.
Dr Adu-Bobie has stated concerns about plating of samples on the bench. The plating from liquid or frozen samples has a risk of producing an aerosol and must be performed in the biological safety cabinet and is set up this way in the MVATL. To perform such an action would be outside of standard laboratory practices, SOP and direct instructions. The plating of solid samples is not considered to pose such a risk. My enquiries did not identify supporting evidence that any laboratory worker performed the action of plating outside of SOPs. My conclusion is that no inference could be drawn from the concerns about plating.
It is noted that ESR undertook DNA analysis of the organism. The first test results found the organism that infected Dr Adu-Bobie was different to that being tested in the laboratory. Follow up tests performed some months later found the two types to be indistinguishable by macro-restriction analysis. This finding presents a learning opportunity for the Department. If, during an investigation, an important piece of evidence is noted to have changed which could have influenced the assessment of the case, then working assumptions should be reviewed in a formal way to determine what impact this could have. In this case it is unclear if this occurred in a planned manner and while it does not appear to have jeopardised the process of the original investigation it may have influenced the strength of the findings.
A report dated 30 June 2008, by Dr Mark Thomas, Associate Professor in Infectious Diseases University of Auckland, commissioned by ACC, looked at the information known about the infection acquired by Dr Adu-Bobie. Dr Thomas concluded that the balance of probabilities overwhelmingly suggests that Dr Adu-Bobie contracted Neisseria meningitidis disease from her work at the ESR laboratory.
The investigation review has confirmed:
- the original DoL investigation collected all the relevant information
- the organism that infected Dr Adu-Bobie was indistinguishable from that under investigation in the laboratory
- in a cluster of five cases caused by Neisseria meningitidis in the Wellington region around the same time as this case only one was of the similar Group B epidemic strain but it could not be adequately characterised
- there is evidence to confirm that the laboratory provided both induction training and supervision
- SOPs in the MVATL were adequate (and despite the level of scrutiny) have remained unchanged
specific variances from SOPs were reported by Dr Adu-Bobie. If they were undertaken they could not be assessed as to their potential to increase risk of infection, and
- no evidence could be found to confirm variation from SOP of plating frozen samples on the bench. Such an action would be a deviation from acceptable international practice and increase the risk of infection.
he Department has responded to e-mail communications and enquiries from Dr Adu-Bobie as official correspondence.
Dr Geraint Emrys, as representative of the Department, met with Dr Adu- Bobie to advise her of the progress of this review, seek clarification of certain points of information and obtain her feedback on the process of this work. Dr Adu-Bobie expressed an overarching desire that learnings from her case result in a decreased risk of other laboratory workers contracting this disease. She advocated particularly for all plating activity to be undertaken in a biological safety cabinet.
There is a need to inform Dr Adu-Bobie of the outcome of this follow-up investigation of her case and should include a copy of this memorandum.
The evidence collected in the original investigation report produced by the Department of Labour on the suspected case of occupationally-acquired disease remains valid.
No specific mechanism of infection has been identified.
This review has attempted to answer a different question to the original investigation including the likely source of infection. It goes beyond the normal work of the Department and any legal test required for enforcement purposes. It has assessed the control measures used to manage the hazard of laboratory-acquired Neisseria meningitidis and the residual risk for infection that exists. It has also assessed the published information on the relative risk of laboratory workers known to have contracted the organism they work with.
The basics of this case include a significant hazard which cannot be eliminated. Appropriate control measures of isolation and minimisation are in place but a residual risk remains. Dr Adu-Bobie contracted meningitis, the same organism present in the laboratory. There is no compelling evidence that this infection was contracted anywhere else. Considering all of the information above my opinion is that on the balance of probability Dr Jeannette Adu-Bobie acquired Neisseria meningitidis infection through her work activity while at ESR Kenepuru MVATL. This conclusion, I believe, also meets the test of being both logical and reasonable.
This opinion is contrary to the conclusion of the Department’s original investigation report.
I acknowledge that this investigation has been prolonged and difficult for the parties involved. ESR have continued to be patient and cooperative through this process despite repeated questioning of an issue that has already been under extensive investigation, I acknowledge the suffering of Dr Adu-Bobie as a result of this terrible infection and her incredible reasonableness and fortitude in dealing with her current situation.
Despite the lack of identification of a mechanism of infection my advice is that there are no further grounds for the Department to revisit this case. The only potential for new information would be fresh declarations or allegations and my investigations have shown no means by which these could be substantiated.
Dr Geraint Emrys
Chief Adviser – Occupational Health