Influenza in immunosuppressed populations: A review of infection frequency, morbidity, mortality, and vaccine response

Pulmonary Section, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.
The Lancet Infectious Diseases (Impact Factor: 22.43). 09/2009; 9(8):493-504. DOI: 10.1016/S1473-3099(09)70175-6
Source: PubMed


Patients that are immunosuppressed might be at risk of serious influenza-associated complications. As a result, multiple guidelines recommend influenza vaccination for patients infected with HIV, who have received solid-organ transplants, who have received haemopoietic stem-cell transplants, and patients on haemodialysis. However, immunosuppression might also limit vaccine responses. To better inform policy, we reviewed the published work relevant to incidence, outcomes, and prevention of influenza infection in these patients, and in patients being treated chemotherapy and with systemic corticosteroids. Available data suggest that most immunosuppressed populations are indeed at higher risk of influenza-associated complications, have a general trend toward impaired humoral vaccine responses (although these data are mixed), and can be safely vaccinated--although longitudinal data are largely lacking. Randomised clinical trial data were limited to one study of HIV-infected patients with high vaccine efficacy. Better trial data would inform vaccination recommendations on the basis of efficacy and cost in these at-risk populations.

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    • "Influenza is responsible for substantial morbidity and mortality worldwide, causing over 250,000 deaths annually [1]. HIV-infected individuals are particularly vulnerable to serious complications of influenza [2, 3], but they have lower serological responses to the influenza vaccine compared to the general population456. While low CD4 cell counts and HIV viremia are important determinants of vaccine response, they do not fully explain the reduced immunogenicity to influenza vaccine observed in this population, indicating that other factors contribute as well [5, 6]. "
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    ABSTRACT: . HIV-infected individuals demonstrate lower immunogenicity to the influenza vaccine, despite immunologic and virologic control of HIV infection. Obesity has been previously shown to be associated with diminished antibody responses to other vaccines in HIV-uninfected persons. However, no studies have examined if obesity is associated with diminished protective immune response to influenza vaccination among HIV-infected persons on antiretroviral therapy (ART). Methods . We performed a retrospective analysis of immunogenicity data from a clinical trial of inactivated, trivalent influenza vaccine. The primary endpoint was the proportion of participants with seroconversion, defined as >4-fold increase in anti-hemagglutinin antibody titers after vaccination. Secondary endpoints were the proportion of participants with seroprotection (defined as antibody titers of ≥1 : 40) and geometric mean hemagglutination inhibition antibody titers. Results . Overall, 48 (27%) participants were obese (body mass index ≥ 30 kg/m 2 ). Seroconversion rates were comparable between obese and nonobese subjects for all three vaccine strains. Further, postvaccination geometric mean titers did not differ by body mass index category. Conclusion . Obesity was not associated with diminished antibody response to influenza vaccination in a sample of healthy HIV-infected persons.
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    • "They also made a large proportion of the individuals at the origin of the evolution of specific triple mutants. In developed countries, an estimated 2% of the population is immunocompromised, and on-going aging and increase in the immunocompromised portion of the human population, including in developing countries, are causes for concern [25,48]. Second, higher replication levels of single and double mutants may represent an important risk for the generation of a virus variant with pandemic potential, along short chains of human-tohuman transmission. "
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    ABSTRACT: Large outbreaks of zoonotic influenza A virus (IAV) infections may presage an influenza pandemic. However, the likelihood that an airborne-transmissible variant evolves upon zoonotic infection or co-infection with zoonotic and seasonal IAVs remains poorly understood, as does the relative importance of accumulating mutations versus re-assortment in this process. Using discrete-time probabilistic models, we determined quantitative probability ranges that transmissible variants with 1–5 mutations and transmissible re-assortants evolve after a given number of zoonotic IAV infections. The systematic exploration of a large population of model parameter values was designed to account for uncertainty and variability in influenza virus infection, epidemiological and evolutionary processes. The models suggested that immunocompromised individuals are at high risk of generating IAV variants with pandemic potential by accumulation of mutations. Yet, both immunocompetent and immunocompromised individuals could generate high viral loads of single and double mutants, which may facilitate their onward transmission and the subsequent accumulation of additional 1–2 mutations in newly-infected individuals. This may result in the evolution of a full transmissible genotype along short chains of contact transmission. Although co-infection with zoonotic and seasonal IAVs was shown to be a rare event, it consistently resulted in high viral loads of re-assortants, which may facilitate their onward transmission among humans. The prevention or limitation of zoonotic IAV infection in immunocompromised and contact individuals, including health care workers, as well as vaccination against seasonal IAVs—limiting the risk of co-infection—should be considered fundamental tools to thwart the evolution of a novel pandemic IAV by accumulation of mutations and re-assortment.
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    • "Influenza virus infection is very common and although usually self-limiting, it remains a significant cause of morbidity in specific vulnerable populations like immunocompromised patients [1] [2]. Treatment with neuraminidase inhibitors is recommended, but viral mutations that reduce susceptibility to oseltamivir occur more often in this group of patients [3] [4]. "
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    ABSTRACT: Immunocompromised patients are at increased risk of complications of influenza virus infection. We report on two critically ill patients on immunosuppressive medication with influenza pneumonia. In both patients, oseltamivir monotherapy did not result in clearance of the virus after 18 and five days, respectively. After adding zanamivir and amantadine to the treatment, PCRs on pharyngeal and/or plasma specimens turned negative in both patients after four and three days, respectively. We suggest, that in critically ill patients with influenza A H1N1 infection, treatment efficacy should be monitored closely and treatment with a combination of antiviral drugs should be considered.
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