Relevant articles were identified by searches of Medline (1966–2009) with the medical subject heading terms “influenza, human”, “influenza A virus”, “influenza B virus”, or “influenza vaccines”, combined with the following associated disease terms: “HIV”, “HIV-1”, “dialysis”, “renal dialysis”, “organ transplantation”, “transplantation”, “bone marrow transplantation”, “neoplasms”, “glucocorticoids”, “adrenal cortex hormones”, “prednisone”, and “prednisolone”. Additional relevant articles
ReviewInfluenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses
Introduction
The influenza virus is among the most common human respiratory viruses. In the USA, for example, influenza can result in the admission of over 225 000 patients to hospital1 and 36 000 deaths every year.2 High rates of influenza infection and complication rates are suggested to occur among people with impaired immune defences. Immunosuppression can result from many different biological mechanisms, ranging from rare congenital immunodeficiencies to more common causes such as immunosuppressive drugs or HIV infection.
Despite prevailing concerns about the risk of influenza infection in patients with immunosuppression, the actual rate and effect of infection in this population are not well characterised. Whether people that are immunocompromised would be even more susceptible to new viruses, such as the recent swine-origin influenza A H1N1 strain,3 without the benefit of previous exposure, is an area for investigation. Moreover, although influenza vaccination is widely recommended for people that are immunosuppressed, the same immune dysfunction that can increase the risk and consequences of influenza infection might also compromise vaccine responses and effectiveness. These distinctions are particularly important in settings of vaccine shortages or in response to a new pandemic, where selective and prioritised allocation of vaccine is necessary. To better inform influenza vaccination policies for immunocompromised populations, we reviewed the published work relevant to influenza infection and vaccination in patients with HIV infection, recipients of solid-organ transplants (SOTs), recipients of haemopoietic stem-cell transplants (HSCTs), patients receiving chemotherapy, patients on chronic haemodialysis, and patients receiving corticosteroids. These conditions affect about 3 million people in the USA (about 1% of the total US population), and the worldwide HIV epidemic affects about 33 million people (table 1).
The primary purpose of this Review is to identify and summarise the incidence and mortality rates of influenza infection among adults who are immunocompromised, as well as the risks of vaccination, the ability of vaccine to elicit appropriate immune responses, and the clinical effectiveness of vaccination in these populations. We also summarise guidelines on influenza vaccination of these populations, limitations of the available data, and alternative approaches to influenza control.
Section snippets
HIV/AIDS
An estimated 1·3 million (480 000 to 1·9 million) people are living with HIV/AIDS in North America. Worldwide, the epidemic affects an estimated 33·2 million (30·6 million to 36·1 million) people.4 Influenza is a common cause of respiratory illness in adults with HIV.10 Because both antibodies and T cells play a crucial part in viral immune responses, patients infected with HIV might be expected have severe and prolonged influenza infections, as reported in several early case series and
Solid-organ transplantation
Patients receiving SOTs are treated with immunosuppressive drugs that alter multiple immune mechanisms.61 Therefore, those patients might have more severe influenza infections and compromised responses to vaccination. As of the end of 2004, 153 245 people in the USA were living with a functioning transplanted solid organ.5 Over 27 000 transplantations are done every year in the USA, nearly 90% of which are kidney, liver, and heart procedures.5
A retrospective review of patients that received
Bone-marrow transplantation
An estimated 35 000 people receive autologous (reimplanted from the same person) and 20 000 allogeneic (from a genetically similar donor) HSCTs every year worldwide.7 Preparation for stem-cell infusion generally requires high doses of chemotherapy, radiation, or both to prevent allograft rejection from residual host immune cells, destroy any residual malignant cells in patients receiving HSCTs for malignancies, and provide marrow space for donor stem-cell engraftment. These intensive
Malignancies and chemotherapy
Some 1·4 million patients will be diagnosed with new haematological and invasive solid-organ cancers in the USA in 2009,8 many of whom will require treatment with chemotherapy. Similar to preparation for HSCT, chemotherapy can produce acute and profound immunosuppression, although the degree differs depending on the chemotherapy drugs, doses, and total duration of therapy. An estimated number of patients receiving chemotherapy every year is not available.
Information about influenza frequency
Haemodialysis
By the end of 2006, 327 754 people were on chronic haemodialysis in the USA, with projected increases in prevalence.6 The complex and multifactorial causes of immune dysfunction in patients on haemodialysis include defects in complement activation, neutrophil function, and B-cell and T-cell function.126, 127, 128 Infections are the second leading cause of death in patients receiving dialysis.6 Compared with the general population, pulmonary infection kills more patients on dialysis129 and
Systemic corticosteroids
Many patients use systemic corticosteroids to treat a wide variety of disorders, particularly inflammatory and autoimmune disorders such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Some patients receive corticosteroids for short periods, whereas others remain on chronic therapy. The prevalence of corticosteroid use is not well known. Of the total British adult population, an estimated 0·9% (or about 409 000 adult Britons) are using oral corticosteroids at any given time,
Limitations and challenges
Among all immunosuppressive conditions discussed, very few data exist on the prevention of clinical influenza infection by vaccination. Most studies have focused on the surrogate outcome of humoral antibody responses. However, a positive humoral response can be defined in multiple ways, most commonly a haemagglutination inhibition titre of 1:40 or greater, or a four-fold or greater rise in titres after vaccination. The limitations of these definitions become apparent, for example, in a patient
Other options to control influenza infection
The priority for control of influenza is focused on generating effective antibody responses with vaccines.13 Progress is being made to increase the scale, duration, and breadth of vaccine responses to haemagglutinin and neuraminidase in healthy and immunocompromised populations.163, 164 Concerns that the cold-adapted live, attenuated vaccine would pose a risk to people that are immunocompromised have proven unfounded so far, but efficacy studies in adults that are immunocompromised have not
Conclusions
We encourage further clinical trials with relevant clinical outcome measures, as opposed to surrogate outcomes like vaccine-induced antibody titres. We would particularly welcome randomised trials comparing standard influenza vaccine with active comparators such as modified vaccines55 or antiviral prophylaxis with or without vaccination. Such data would greatly enhance our ability to make more informed vaccination recommendations for this population, particularly in situations of vaccine
Search strategy and selection criteria
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