Theme 1. Primary prevention
1.1 Vaccinology
Patients lose protective antibodies following allogeneic BMT, but data on vaccine immunogenicity and efficacy are inadequate and vaccines underutilized (Henning K et al., JAMA, 1997; 277:1148). Published studies of donor-recipient vaccination to improve recipient immunity have focused on sibling donors. Although infection risks are higher after unmatched BMT, there has been a reluctance to impose unnecessary interventions on unrelated donors. There are several newly licensed bacterial and viral vaccines that have the potential to prevent infection in BMT patients, but which have not been studied in this high-risk population.
1.1.1 Vaccine efficacy & immunogenicity in BMT recipients and donor-recipient vaccination
(CIs MacIntyre, Gilbert, Gottlieb, Dwyer; AIs Shaw, Gilroy; Collaborators: Sullivan, Abendroth) Tiin BMT recipients
Randomised, placebo-controlled (RCT) trials of immunogenicity of pneumococcal conjugate (PCV7, years 1&2) and Varicella (VZV) (years 3&4) vaccines. We will measure fntibodies to pneumococcal vaccine serotypes and cell-mediated immune responses to VZV in recipients, donors immunized pre-transplant and controls, before and 6 & 12 months after immunization. 132 subjects per vaccine group will allow comparison of reactogenicity (local reactions and fevers at 3 & 7 days post vaccination) and response rates between groups with 95% confidence intervals; 120 allogeneic BMT are performed each year in the BMT Network.
1.1.2 Limits of altruism - will BM and blood stem cell donors participate in research?
(AI Jordens, CIs Kerridge, Ankeny, MacIntyre, Bradstock, Gottlieb, AI Shaw)
Aim To examine attitudes, beliefs and values of BM donors regarding the act and limits of donation and the role and extent of research incorporating unrelated donors. Method Surveys of Australian BM Donor Registry (ABMDR) unrelated donors and sibling donors and in-depth interviews with 5-10 ABMDR donors and 5-10 sibling donors. Note: This study will be completed before unrelated donors are approached for the immunogenicity study in 1.1.1.
1.2 Respiratory precautions
(Aims 1-3: AIs Gilroy, Shaw, Corbett; CIs Dwyer, Gilbert, Bradstock; Collab. Tovey; Aims 4,5: AI Selgelid; CIs Kerridge, Ankeny; AIs Gilroy, Shaw, Lumby, Jones)
Background Infections with community respiratory viruses (CRVs) e.g. respiratory syncytial virus (RSV), parainfluenza, influenza A/B, adenoviruses and rhinoviruses, occur in 10% of BMT recipients at Westmead Hospital; 63% are hospital-acquired and 28% fatal (retrospective data). Antiviral agents have limited efficacy. The roles of newer human metapneumovirus (hMPV) and coronaviruses (hCV) in HSCTs are unknown. Evidence exists that survival & transmission of CRVs in droplets varies with environmental conditions, eg temperature, humidity. Measures to reduce CRV transmission raise issues (eg isolation, screening and reduced visitor access -especially of dependent children or parents of paediatric patients) that may adversely affect patients or staff.
Aims 1) Deve1op & evaluate interventions to reduce CRV transmission in haematology wards. 2) Investigate the role of hMPV in lower respiratory illness. 3) Develop methods to investigate effects of hospital atmospheric conditions on survival of airborne viruses. 4) Examine scientific, ethical, professional and sociopolitical issues underpinning institutional respiratory infection control policies. 5) Examine issues relating to use of potentially teratogenic aerosolised ribavirin. Methods 1) For this longitudinal, population-based, study, we will develop a BMT Network-based surveillance tool, incorporating standard clinical and laboratory case definitions, protocols for laboratory testing, reporting of results and data analysis of CRVs. Intervention Develop and implement an educational module, in consultation with stake-holders (patients, close contacts & hospital staff) to raise awareness of CRVs, promote influenza vaccination and compliance with respiratory and contact precautions. Primary endpoints: influenza vaccine uptake; compliance with infection control precautions; incidence, morbidity and mortality from CRVs (compared with baseline). 2) Collect nasopharyngeal & bronchial specimens from patients with respiratory symptoms; test for respiratory viruses including hMPV and hCV, using an in-house PCR; document incidence, clinical (including long-term shedding) and imaging features of hMPV and hCV infection. 3) Evaluate current technologies (air samplers, UV lights, ionisers) for assessment of viral concentrations in air in hospitals and to gauge the effectiveness of engineering and ventilation controls in reducing airborne viral transmission in the hospital environment 4) Use literature review, text analysis and philosophical examination of issues such as tension between public and private good, impact of quarantine and restriction of personal and occupational freedom on health grounds, to inform respiratory infection control policy – ( see Aim 1). 5) Survey ribavirin policies in Australian BMT units; qualitative analysis (focus groups) of views of nursing, medical and occupational health & safety (OHS) staff; literature review of post-transplant RSV infection and OHS aspects of aerosolised ribavirin use.
