Hepatitis C Virus in a Scottish Emergency Department

Transcription

1 Environmental Transmission of Hepatitis C Virus in a Scottish Emergency Department Ingólfur Johannessen NHSL Laboratory Medicine 2016 Overview Background Hepatitis C virus (HCV) Laboratory diagnostics Incidents Epidemiological Investigations Initial Hypothesis Molecular Investigations Infection Prevention & Control Review Hypothesis Summary & Conclusions Relevance Page 1

2 Background Background - 1 Several reports of hepatitis C virus (HCV) transmission from healthcare workers (HCWs) to patients in the context of exposureprone procedures (EPP) as well as from HCV-infected patients to HCWs following exposure incidents HCV transmission in the hospital setting has been reported with use of contaminated equipment (eg, needles/syringes and haemodialysis machines), medication (eg, multi-dose vials and infusion bags) and environment Such events are very rare and usually reflect one-off transmissions Page 2

3 Background - 2 Fully implemented infection prevention and control (IPC) measures should prevent HCV transmission within healthcare systems thereby ensuring patient safety HCV infection in the healthcare setting is often undetected due to the asymptomatic nature of most acute HCV infections Two HCV transmission incidents occurred at the same Scottish hospital in 2013; its Emergency Department (ED) is the busiest in Scotland and one of the busiest in Europe Hepatitis C Virus (HCV) Page 3

4 Hepatitis C Virus - 1 Small enveloped ss+rna hepacivirus Member of flaviviridae family; identified in 1989 Infects hepatocytes and, to extent, lymphocytes Transmits through contaminated blood (eg, IVDU) and, to a much lesser degree, other body fluids 6 main genotypes ( genotype 1-6 ) and over 50 subtypes ( a-n ) with evidence emerging for further genotypic divisions of the virus Genotypes 1-3 are found world-wide and, in line with the rest of Northern Europe (and North America), HCV genotype 1a is the most common genotype in the UK Hepatitis C Virus million HCV carriers globally (WHO data); 10-40% without identifiable risk 4 million carriers in Europe (population prevalence ranges from 0.4-3% in Europe) The prevalence of HCV carrier state t in England is estimated t to be around 0.4% of the population - but the prevalence in Scotland is considerably higher at an estimated 1% of the population Page 4

5 Hepatitis C Virus % of infected individuals clear HCV infection within first 6 months; remainder suffers chronic infection 60-70% of chronically infected individuals (when not treated) develop chronic liver disease; 5-20% of patients develop liver cirrhosis over a period of years; up to 20% of patients with HCV cirrhosis may develop hepatocellular carcinoma (HCC) 20-30% of HCV-infected individuals develop acute HCV hepatitis within 4-12 weeks that may prompt presentation to health care services; up to 50% of such individuals experience spontaneous virus clearance Evidence suggests that HCV may linger in infected hepatocytes Hepatitis C Virus - 4 Treatment options include interferon-α and/or ribavirin therapy with/without new protease inhibitors (PIs) and/or additional novel antiviral agents; fast becoming a largely curable infection but at a high financial cost No vaccine available Post-exposure prophylaxis (PEP) is not offered although novel therapy may change the approach Au & Pockros; Clinical Pharmacology & Therapeutics advance online publication 27 November 2013; doi: /clpt Page 5

6 Laboratory Diagnostics Laboratory Diagnostics Serological assays HCV antibody EIA HCV antigen EIA HCV avidity EIA Molecular assays HCV NAAT (ie, PCR) HCV sequence analysis Page 6

7 Acute HCV Infection An acute illness with identifiable onset of any sign/symptom consistent with acute (viral) hepatitis together with elevated/rising serum ALT (>100 IU/L) that is confirmed by laboratory HCV tests to reflect recent virus acquisition (detection of virus genome and core protein in blood of a HCV antibodyseronegative individual followed by antibody seroconversion) The laboratory test panel should include HCV antigen, HCV viral load (VL) and HCV antibody assessments of a suspected case of acute HCV hepatitis that is not known to be a HCV carrier Incidents Page 7

8 Incidents Case 1 Spring 2013 Recent HCV acquisition diagnosed following routine blood- borne virus (BBV) screening; did not develop symptomatic ti or biochemical hepatitis Frequent hospital admissions associated with complications of end-stage renal failure and long-term home haemodialysis Case 2 Autumn 2013 Recent HCV acquisition diagnosed following routine GP health checks that showed a raised liver function test (LFT); developed asymptomatic biochemical hepatitis Incident Management Team (IMT) established in spring 2013 No behavioural risk factors were identified Both cases were subsequently shown to harbour HCV genotype 1a Epidemiological Investigations Page 8

9 Epidemiological Investigations Investigations included all healthcare contact from 4 weeks prior to last HCV antigen negative sample (Case 1) 6 months prior to first test showing raised LFT (Case 2) Medical records were reviewed to trace patients journeys (incl dates of admission, diagnostic procedures, surgical interventions, medications and other treatments) Timelines were constructed and patient locations assessed using floor plans available from electronic records Monthly HCV testing for all haemodialysis patients for 3 months (Case 1); no further cases identified Findings Case 1 Attended the hospital several times for reasons associated with underlying clinical condition; admitted through ED to renal unit (assessments in vascular theatres and catheter laboratories) Received blood transfusions during the period under investigation (all donations re-tested HCV PCR-negative) Case 2 Attended ED on one occasion only for an overnight stay for observation; procedures undertaken included cannulation, venepuncture, arterial blood gases and single administration of iv anti-emetic agent Had not received blood transfusions Neither case had undergone EPP Page 9

10 Initial Hypothesis Initial Hypothesis On balance of probabilities, investigators considered the most likely virus sources to be HCV-infected patients that had attended the same hospital clinical areas at a similar time as the cases It was postulated that HCV-infected blood had been transferred from sources through blood contamination of environment, equipment and/or hands of HCWs An HCV-infected HCW as a virus source was considered less likely as the risk of patient-to-patient to transmission is considered to be greater than the risk of HCW-to-patient transmission Importantly, neither case had undergone EPP so HCWs were not offered HCV antibody tests Page 10

11 Molecular Investigations Molecular Investigations Permissions obtained from the Tissue Governance Authority and Caldicott Guardian Patients that attended the same clinical areas 12 hours prior to, and up to 4 hours following, case admission, were cross-matched against the Scottish national HCV diagnoses database; later extended to 7 days prior to admission to, and up to time of discharge from, a particular clinical area Deterministic linkage on sex, date of birth, initials and soundex code of surname was used Stored residual diagnostic samples from matches were identified and used for phylogenetic analyses wherever possible Page 11

12 Phylogenetic Analysis Core antigen Genotype Sequence analysis NS5B E2 Hypervariable region (HVR) Findings - 1 Case 1 Genetic testing showed that none of the 5 known HCV-infected haemodialysis patients managed in the hospital s renal unit at the time carried related virus 2,952 patients were admitted in the 12hrs prior to, and up to 4hrs following, case admission to the hospital s clinical areas; 23 patients were identified as having an active HCV infection of unknown or genotype 1 virus; all were unrelated to case 1 9,943 patients were admitted 7 days prior to, and up to the time of discharge from, clinical areas; additional 22 patients were identified as having an active HCV infection of unknown or genotype 1 virus; all were unrelated to case 1 Taken together, a virus source was not identified and that remains the case to this day Page 12

13 Findings - 2 Case 2 9 HCV-positive patients were admitted in the 12hrs prior to, and up to 4hrs following, case admission to the hospital s ED 6 of these 9 patients were identified as having active HCV infection, of which 4 were known to have an unknown or HCV genotype 1 infection Phylogenetic analyses demonstrated a complete sequence match with one of the known genotype 1 patients Taken together, scientific and spatio-temporal temporal evidence supported the identification of a virus source The source patient s stay in the ED had overlapped with that of Case 2 by 45 minutes Examination of the source patient included manual examination of superficial wounds, blood tests and blood gas analysis Phylogenetic Analysis Core Ag Case a.H a.GB.Glas a.S6b.AJ5 73 1c.ID.YS11 1b.JP.TMOR 100 1b.DE.NC b.IT.I d D 99 4d.AR.AR46 4c.GA.GB a.EG.ED43 4a.AR.AR b.JPUT b.JP.HC-J 100 2b.MD2B-1. 2c.FR.FR a.JP.AY74 2a.FR.FR7. 6a.HK.6a c.NP.NE04 3b.IN.NB a.DE.HCVC 3a.TH.TH a.PK.3aPK 5a.ZA.SA13 Page 13

14 Phylogenetic Analyses NS5B and E2 HVR Case 2 Infection Prevention & Control Review Page 14

15 Infection Prevention & Control Review Infection Prevention and Control Nurse (IPCN) specialists used available timelines to review relevant clinical areas and carry out inspection of environment and clinical equipment Practice and compliance with national IPC guidance was observed Clinical staff was interviewed informally on the use of Standard Infection Control Precautions (SICPS ) and encouraged to identify any points of patient care pathway that might have posed transmission risk Senior staff in each area facilitated a walk-through of each case patient s journey to identify potential areas of cross-over and transmission risk Case 2 Timeline Page 15

16 Findings Compliance with national IPC guidance was observed across all clinical areas with the exception of the hospital s ED In the ED, the IPCN specialists observed an extremely busy environment with design limitations that did not facilitate compliance with SIPCP patients receiving treatment out-with treatment areas non-compliance with use of personal protective equipment (PPE; prolonged use, and inadequate change, of gloves); hand hygiene; decontamination of communal equipment that hand hygiene sinks were limited and difficult to access that whilst alcohol gel was available within treatment areas, there was often no alcohol gel at the point of patient contact out-with such areas Floor Plan of ED Page 16

17 Hypothesis Hypothesis Case 2 and virus source overlapped for a period of 45 minutes in ED; time lag between blood gas analyses of case and source was 3 hours and 55 minutes; blood gas analyser (BGA) was located directly adjacent to ED clean iv preparation area Upon inspection, BGA (touch control panel and its environment) was noted to be contaminated with visible small blood spatter Repeatedly, it was observed that staff failed to remove gloves before or after operating the BGA Alternative explanations and on-going transmission were ruled out following a subsequent patient notification exercise (34 patients) that identified and tested patients considered to have been at similar risk; 31 tested and found to be HCV antibody negative Page 17

18 Summary & Conclusions Summary and Conclusions To our knowledge, this is one of the first investigations to provide evidence of HCV transmission in the ED setting No virus source of Case 1 s infection was identified Virus source of Case 2 (high HCV load) underwent a limited number of invasive procedures that could only have provided a route of entry if there had been a concomitant IPC failure Exact transmission route could not be determined; the most plausible explanation was surface blood contamination of shared equipment particularly, the unit s BGA It is possible, that the transmission event surrounding Case 1 occurred in the same ED possibly through similar mechanisms NHSL offered its apologies to both Case 1 and Case 2 Page 18

19 Relevance Relevance The identification of 2 unrelated HCV transmission events in such a short time period associated with a single hospital is highly unusual Documented transmission of HCV through surface blood contamination of equipment is also unusual though similar incidents have been described in the haemodialysis setting The combination of a high prevalence of infection (and levels of undiagnosed infection) among the populations attending EDs and increasing pressures on the physical and/or staffing capacities in these settings, will continue to test the extent to which the environment, equipment and staff behaviour can maintain IPC standards to protect against BBV transmission Page 19

20 Acknowledgments Acknowledgements Agencies represented on the Incident Management Team: NHSL Laboratory Medicine NHSL Health Protection Team NHSL Infection Prevention & Control Service NHSL Occupational Health Service NHSL Department of Renal Medicine NHSL Regional Infectious Diseases Unit University of Edinburgh Infection Prevention & Control, Health Protection Scotland Blood-Borne Virus Group, Health Protection Scotland Scottish National Blood Transfusion Service Scottish Ambulance Service Page 20

21 Thank you! Page 21