On 21st December 2012 commenced an investigation into the death of Craig Adam Unit 1 , Gilbert Drive, Endeavour Park, Boston PE21 7TQ Tel: 01522 553374 Fax: 01522 516717 Email: HMCoroner_Southlincolnshire@lincolnshire gov.uk

A RW Forrest LLM, FRCP, FRCPath GMC Number: 1333523 Her_Majesty's Senior Coroner for South Lincolnshire_ WHITE, age 21. investigation concluded at the end of the inquest on 10" January 2014. The conclusion of the inquest was MISADVENTURE due to disseminated tuberculosis_

Craig Adam White was a 21 year old student; in his final year at Lincoln University. He was born and brought up in Lincolnshire, an area with a low incidence of tuberculosis. He received BCG immunisation as a child. He developed Crohn's disease at the age of
16. Eventually control of the disease was achieved with a regimen that included treatment with Azothioprine and infusions of Infliximab every 8 weeks. Infliximab was administered in hospital by a nurse on a gastro-intestinal ward: A letter was not sent to Craig's general practitioner after each infusion: Infliximab is a monoclonal antibody which inhibits the activity of the Cytokine Tumour Necrosis Factor Alpha. This blocks part of the pathological mechanism of Crohn's disease, but also inhibits the body's response to infection and, in particular Tuberculosis, Because the was prescribed and administered entirely by secondary care practitioners, it did not appear on the System One Home screen that would be consulted when Craig consulted his primary health care providers. Before starting treatment with Infliximab he had been screened for latent tuberculosis by Chest history his BCG immunisation scar being noted. His Crohn's disease was proven and review of the biopsies after his death confirmed the diagnosis and excluded his gastro-intestinal illness being an atypical presentation of tuberculosis_ From September 2012 onward Craig presented to the University Health service at Lincoln with recurrent chest infections He did not see a registered medical practitioner there. The experienced nurse practitioner / independent nurse provider who saw him on several occasions gave evidence that she knew Craig was on Infliximab, that she knew it was a immunosuppressant but did not know of the increase risk it posed of tuberculosis. At the inquest she took roughly 7 minutes to find the relevant section (10.1.3) of the British Tel: 01522 553374 Fax: 01522 516717 Email: HMCoroner_Southlincolnshire@lincolnshire gov.uk The good drug - X-ray, and biopsy '

A R W Forrest LLM, FRCP, FRCPath GMC Number: 1333523 Her Majesty's Senior Coroner for South _Lincolnshire National Formulary that draws attention to the increased risk of tuberculosis. Craig did not respond to first line antibiotic treatment for his chest infection; Treatment with two secondlthird line antibiotics, Clarithromycin and Ciprofloxacin; which have some limited activity against tuberculosis, produced temporary improvement in his condition; On 31st October 2012, Craig consulted a general practitioner with 10 years experience in Boston (Lincolnshire) with a of recurrent chesty cough: a subset of Craigs clinical record was available on the System One E-records available to the GP. Craig told the GP that he was being treated with Infliximab and Azothioprine for his Crohn's disease. The GP gave evidence that he was aware of the association of treatment with Infliximab and tuberculosis He was aware from his own practice of the very low incidence of TB in those born and brought up in Lincolnshire_ He arranged for blood tests including full blood count; urea and electrolytes and a C-reactive protein and a Chest X-Ray: These showed a raised C reactive protein, a low white blood cell count;,a marginally reduced plasma sodium and a small right sided pleural effusion. The doctor decided to prescribe a 3rd line antibiotic (Ciprofloxacin) to wait and see if the clinical picture improved On 30h November Craig became acutely ill, he was confused; he fitted in the Accident and Emergency department at Pilgrim Hospital and was taken to the Intensive Unit; After a CT scan, done primarily to establish it was safe to perform a lumbar puncture, a lumbar puncture was done This only showed a small elevation in protein concentration. Craig was sedated and treated with antibiotics and the anti-viral drug Acyclovir; The following day he was extrubated and transferred to a general medical ward, Whilst there, he had a fluctuating level of consciousness. An MRI done on 5th November 2012 showed changes suggestive of Leptomeningitis. He was prescribed further antibiotics, including Co-trimoxazole. A further CT scan was done on 9th December 2012. Again this was primarily to assess the safety of a lumbar puncture On this occasion the tests requested on the CSF included a Polymerase Chain Reaction Tel: 01522 553374 Fax: 01522 516717 Email: HMCoroner_Southlincolnshire@lincolnshire gov.uk history ' Only = and Therapy

A RW Forrest LLM, FRCP, FRCPath GMC Number: 1333523 Her Majesty's Senior Coroner for South Lincolnshire_ (PCR) test for tuberculosis_ Specific treatment for tuberculosis meningitis was not initiated at that point Craig was readmitted to the ITU on gth December 2012. Review by Intensivists, Gastroenterologists and a Neurologist on guh and 10th December 2012 produced a differential diagnosis of Multi-Focal Leukeoencephalopathy, Listeria Meningitis, Crytococcal Meningitis, TB Meningitis and Aseptic Meningitis. Amphotericin was added to his treatment. Specific treatment for tuberculosis was not administered: Evidence was given that at that point "Gold Standard" treatment for tuberculosis meningitis would have had a less than 80% chance of resulting in Craig's survival: Craig's condition deteriorated and at 17.30 hours on 12th December 2012, just before the first set of tests to confirm a diagnosis of Brain Stem Death were to be carried out; the consultant Intensivist received a call the Microbiology Laboratory informing him that positive result for tuberculosis had been found on PCR testing of the cerebro-spinal fluid sample obtained on 9t December 2012. At Post Mortem Craig was found to have widely disseminated tuberculosis in his chest and abdomen as well as Tuberculosis Leptomeningitis, early Cerebritis and abscess formation in his brain with an acute thrombosis in the sigmoid sinus. An epidemiological investigation by Public Health England has not revealed how Craig came to be infected with tuberculosis.

In my opinion action should be taken to prevent future deaths and believe you andlor your organisation have the power to take such action.