INFLUENZA VIRUS INFECTIONS IN TRANSPLANT RECIPIENTS: A MULTICENTER REGISTRY

There is limited prospective data on influenza infections in transplant
recipients. However, influenza can be a significant cause of morbidity and
mortality in some organ transplant populations. Reported attack rates have
varied considerably and are likely due to differences in transplant
populations, immunosuppression protocols, exposures, and type and virulence of
circulating influenza viruses. Complications of influenza infection appear to
be common in hematopoietic stem cell transplant (HSCT) and solid organ
transplant (SOT) populations. There appears to be a relatively high rate of
progression to viral pneumonia in some reports especially in lung transplant
recipients and HSCT recipients. In one study of organ transplant recipients
over a 10-year period, the rate of influenza infection ranged from 2.8
cases/1000 person years (liver transplant) to 41.8 cases/1000 person years
(lung transplant). Complications including secondary bacterial pneumonia (17%)
as well as extrapulmonary complications such as myocarditis, and myositis were
observed. This is in contrast to a report by Ljungman et al. of 12 influenza
cases in renal transplant recipients. Only one patient developed viral
pneumonia and one had bronchitis. The remaining 10 patients recovered without
complications.

The largest study in the SOT population was done during 2009-2010 outbreak of
pandemic H1N1 by the American Society of Transplantation (AST) H1N1
Collaborative Group. This was a retrospective review of 237 patients with
pandemic H1N1 infection and included both adults and pediatric patients. The
majority of the patients reported in the study were hospitalized (70%) and 15%
were admitted to the intensive care unit. Approximately one-third of patients
had pneumonia at presentation. Death occurred in 4% of patients. Early
initiation of antiviral therapy was associated with decreased hospitalization,
ICU admission and a lower risk of death.

Despite the recognized importance of influenza in transplant patients, there is
actually very limited prospective data. This registry will represent the
largest prospective data collection on influenza in transplant patients and
will provide invaluable data on the clinical presentations, antiviral efficacy
and other parameters related to influenza.

• Our purpose is to prospectively characterize influenza infections over a 3
year period in transplant patients using a registry system.
• We plan to generate robust data on clinical features of upper and lower
respiratory disease, antiviral therapy and its effects on disease outcome, as
well as quantitative virologic data on shedding and antiviral resistance.
• We also will study the long term sequelae of influenza infections and look at
development of rejection.

This will be a prospective, multi-center study conducted at investigator sites
who comprise the Influenza in Transplant collaborative study group. This
includes over 30 centers from across North America and Europe. The
co-ordinating center will be the University of Alberta. We will aim to enrol
300 patients in the registry over a 3 year period.

The following information will be gathered:

a) Clinical Information
- Baseline demographic information about the transplant (including
immunosuppression, graft function)
- Comorbidities such as diabetes, obesity, chronic lung disease
- Symptoms of infection, radiologic features of infections
- Antiviral use
- History of vaccination
- Outcomes such as hospitalization, ICU admission, mechanical ventilation, death
- Long term outcomes: allograft function, chronic respiratory disease
- Laboratory parameters including lymphocyte count, immunoglobulin levels,
renal function
- Adverse events - all serious adverse events occurring during the study (till
day 180) will be reported. These include: a) hospitalization; b) congenital
deformity; c) death; d) disability; and e) other adverse events the
investigator considers serious. Pregnancy during the follow-up period will
also be reported.


b) Virology
- Method of diagnosis (DFA, viral culture, PCR)
- Subtype of influenza virus (ie HxNx)
- Viral Shedding by serial NP swabs at day 0 (diagnosis), 3, 6, 11, 18, 28
(weekly thereafter if shedding persists)
- Quantitative PCR of NP swabs (centrally at University of Alberta)
- Antiviral resistance testing at first and last positive swabs


c) Immunology
- Serum collection at disease onset and 4-6 weeks afterwards for
o Serology against circulating influenza viruses
o Production of HLA alloantibodies

Possible Benefits:
It is not known whether there will be direct benefit from being in the study.
However, the information learned in this study may
help other patients with similar conditions in the future.

Possible Risks:
Taking blood is briefly uncomfortable, but not dangerous. When having blood
drawn, participant may have some bruising where it is
taken. This may take several days to go away. Every effort will be made so that
blood will be collected for the study at times when
subjects are having other routine blood tests.