Incidence and characteristics of the 2009 influenza (H1N1) infections in inflammatory bowel disease patients

BackgroundIn 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009–2010.MethodsA multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10 months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections.ResultsA total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20 years was significantly higher than that among patients in other age groups (p < 0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7 days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group.ConclusionOur prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed.     

Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis

Objective

To evaluate the influence of abatacept (ABA) and associated contributing factors on pandemic 2009 influenza A/H1N1 vaccine immunogenicity in rheumatoid arthritis (RA) patients.

Methods

The response to a nonadjuvanted monovalent pandemic 2009 influenza A/H1N1 killed virus vaccine was analyzed in 11 RA patients using ABA (RA‐ABA), most with concomitant nonbiologic disease‐modifying antirheumatic drugs (DMARDS), and compared to 33 age‐matched RA patients on methotrexate (MTX) and 55 healthy controls, all without previous seroprotection. Clinical and laboratory evaluations were performed before and 21 days after vaccination. Anti‐influenza antibody titers were measured by hemagglutination inhibition assay. Seroprotection (antibody titers ≥1:40) and the factor increase (FI) in the geometric mean titers (GMTs) were calculated. Prevaccination lymphocyte counts and gammaglobulin levels were determined.

Results

Sex distribution, disease duration, and the Disease Activity Score in 28 joints were similar in the RA groups (P > 0.05). After vaccination, seroprotection was significantly reduced in RA‐ABA patients compared to RA‐MTX patients (9% versus 58%; P = 0.006) and controls (69%; P ≤ 0.001). FI‐GMT was severely reduced in RA‐ABA patients compared to RA‐MTX patients (1.8 [1.4–2.3] versus 8.7 [5.2–17.4]; P < 0.001) and controls (11.5 [8.0–16.7]; P ≤ 0.001). Lymphocyte counts were comparable in RA groups (P > 0.05), but RA‐ABA patients had slightly lower gammaglobulin levels than RA‐MTX patients (0.9 gm/dl [0.6–1.8] versus 1.2 gm/dl [0.8–1.7]; P = 0.03), although almost all were within the normal range values.

Conclusion

The current study established that ABA, in association with traditional DMARDs, significantly reduces the humoral response to pandemic 2009 influenza A/H1N1 vaccine in RA patients. The results suggest an influence of costimulatory modulation in humoral response to this vaccine.     

Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease

Vaccines have undoubtedly brought overwhelming benefits to mankind and are considered safe and effective. Nevertheless, they can occasionally stimulate autoantibody production or even a recently defined syndrome known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is scarce data regarding autoimmune response after seasonal/influenza A (H1N1) vaccine in patients with autoimmune inflammatory rheumatic disease (AIRD). The objective of our study was therefore to determine autoimmune response in a large group of AIRD patients vaccinated against seasonal and/or H1N1 influenza. We conducted a prospective cohort study with a 6-month follow-up. Two-hundred and eighteen patients with AIRD (50 vaccinated against seasonal influenza, six against H1N1, 104 against both, 58 non-vaccinated controls) and 41 apparently healthy controls (nine vaccinated against seasonal influenza, three against H1N1, 18 against both, 11 non-vaccinated controls) were included. Blood samples were taken and screened for autoantibodies [antinuclear antibody (ANA), anti-extractable nuclear antigen (anti-ENA), anticardiolipin (aCL) IgG/IgM antibodies, anti-beta 2-glycoprotein I (anti-β2GPI)] at inclusion in the study, before each vaccination, 1 month after the last vaccination and 6 months after inclusion. For non-vaccinated participants (patients and healthy controls) blood samples were taken at the time of inclusion in the study and 6 months later. We report that after the administration of seasonal/H1N1 vaccine there were mostly transient changes in autoantibody production in AIRD patients and in healthy participants. However, a small subset of patients, especially ANA-positive patients, had a tendency towards anti-ENA development. Although no convincing differences between the seasonal and H1N1 vaccines were observed, our results imply that there might be a slight tendency of the H1N1 vaccine towards aCL induction. Although seasonal and H1N1 vaccines are safe and effective, they also have the potential to induce autoantibodies in selected AIRD patients and healthy adults. Follow-up of such individuals is proposed and further research is needed.     

Hepatitis B vaccination in patients with inflammatory bowel disease

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD).METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination.RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313).CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.     

An audit of influenza vaccination status in adults with inflammatory bowel disease

BACKGROUND

Several guidelines recommend influenza vaccination for high-risk patients, including those on immune-suppressing medications (IS).

OBJECTIVE:

To assess the vaccination status and immunization history of an outpatient inflammatory bowel disease (IBD) population for H1N1 and seasonal influenza.

RESULTS:

Among 250 patients, 104 (41.6%) had been immunized against H1N1 and 62 (24.8%) against seasonal influenza, and 158 (63.2%) were taking IS (azathioprine, 6-mercaptopurine, infliximab, adalimumab, methotrexate, cyclosporine or prednisone). Among subjects on IS, the presence of comorbidities warranting vaccination was associated with higher likelihood of H1N1 immunization (62.5% versus 35.8%; P=0.022) but not of seasonal influenza vaccination (25.0% versus 17.2%; P=0.392). Among patients without comorbidities warranting vaccination, IS was associated with a decreased likelihood of vaccination against seasonal influenza (17.2% versus 30.7%; P=0.036) but not H1N1 (35.8% versus 41.3%; P=0.46). The frequency of H1N1 vaccination was significantly higher among patients who visited a general practitioner at least once yearly (45.7% versus 20%; P=0.0027), with a similar trend for seasonal influenza vaccination (27.1% versus 12.5%; P=0.073). Among 91 patients on IS who declined vaccination, 39.6% reported fear of immediate side effects, 29.7% reported concerns about developing serious medical complications, 15.4% reported concerns about activating IBD and 15.4% were not aware that vaccination was indicated.

CONCLUSIONS:

Current strategies for vaccinating IBD patients on IS are inadequate. Primary care provider education, incentive programs and regular primary care contact may improve immunization uptake.     

Adverse events associated with the 2009 H1N1 influenza vaccination and the vaccination coverage rate in health care workers

We prospectively examined the 2009 H1N1 influenza vaccination coverage rate and the adverse events related to the monovalent vaccine in Korean health care workers. The H1N1 vaccination coverage rate was 91.7%. There were no significant adverse events discouraging the vaccination.     

Cytokine response in pediatric patients with pandemic influenza H1N1 2009 virus infection and pneumonia: comparison with pediatric pneumonia without H1N1 2009 infection

Objectives

We investigated serum cytokine levels in pediatric patients with pandemic influenza H1N1 2009 virus (H1N1) infection‐pneumonia and in pediatric patients with pneumonia but without H1N1 infection, and examined correlations between cytokine levels and clinical/laboratory findings.

Methods

Fifty‐seven cases of infection by H1N1 were confirmed by RT‐PCR and enrolled. Of these 57 cases, 26 had a severe H1N1 infection (group 1), and 31 had a mild H1N1 infection (group 2). Sera from 18 cases with pneumonia without H1N1 infection (group 3) were used as controls. The serum levels of 10 cytokines were determined by multiplex assay.

Results

The serum levels of IFN‐α, IL‐6, and IP‐10 were significantly higher in H1N1 infected cases than in group 3, and levels of IL‐6 and IP‐10 were significantly higher in group 1 than in group 2. The level of IL‐10 was significantly higher in groups 1 and 3 than in group 2. However, levels of IFN‐γ and IL‐17 were not significantly different between the three groups. IL‐1β, IL‐4, and MIP‐1α were not detectable in most patients. IP‐10 and IL‐6 levels were found to show negative correlations with lymphocyte count and oxygen saturation.

Conclusions

We found higher levels of cytokines (IFN‐α, IL‐6, IP‐10) of innate immunity than those of acquired immunity in pediatric H1N1 infection. Of the cytokines found to be increased in cases with H1N1 infection, IP‐10 and IL‐6 were found to be correlated with disease severity (lymphopenia and hypoxia). IP‐10 and IL‐6 may be important markers in pediatric H1N1 infection. Pediatr Pulmonol. 2011; 46: 1233–1239. © 2011 Wiley Periodicals, Inc.

     

Isolation of Aspergillus in three 2009 H1N1 influenza patients

OBJECTIVES: To describe the association of Aspergillus with influenza. DESIGN/SETTING/SAMPLE: Three case reports of ICU patients with influenza complicated by the isolation of Aspergillus species are described and a review of the literature on the topic was performed. CONCLUSIONS: Severe influenza cases can be complicated by Aspergillus infection.     

Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients

Please cite this paper as: Couturier et al. (2010). Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients. Influenza and Other Respiratory Viruses 4(4), 199–204. Background First-line treatment of influenza A 2009 H1N1 relies on neuraminidase inhibitors such as oseltamivir. Resistance conferred by the H275Y neuraminidase gene mutation is concerning and likely to increase. Objectives To characterize oseltamivir resistance in a hospital-based patient population. Patients and Methods All available respiratory specimens positive for influenza A by direct fluorescent antibody, RT-PCR, or culture from patients at the University of Utah 5/09-12/09 were collected. Specimens were confirmed as 2009 H1N1 by the Utah Department of Health. RT-PCR and pyrosequencing were used to test for the H275Y mutation (CDC protocol). Pyro Mark Q24 AQ software (Qiagen, Valencia, CA, USA) was used to allow for quantitative H275Y mutation analysis. Medical records of patients with resistant virus were reviewed. Results We tested 191 influenza A virus-positive samples from 187 unique patients. Fifty (27%) patients were hospitalized. Four patient specimens (2·1%) were found to carry the H275Y mutation. Three patients were hospitalized, representing 6% of inpatient samples tested. Three patients had undergone hematopoietic stem cell transplant in the past year. Two patients died. Their influenza viruses were confirmed to be oseltamivir-resistant at an independent reference laboratory and through the Center for Disease Control and Prevention (CDC). One patient reported no history of prior oseltamivir exposure. Conclusions Widespread oseltamivir resistance among 2009 H1N1 remains a potential threat. Rapid techniques, such as pyrosequencing, which has the additional benefit of identifying mixed mutant populations of virus, may play a key role in identifying at-risk individuals and potentially unsuspected cases. Targeted surveillance of immunocompromised patients will be critical toward improving future influenza planning and therapy.     

Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment

Cancer patients are often encouraged to receive seasonal influenza vaccination. The monoclonal antibody rituximab is widely used in treatment of non-Hodgkin lymphoma. This results in a prolonged depletion of normal B cells, which might impair humoral responses. The aim of the present study was to investigate whether lymphoma patients undergoing rituximab-containing treatment regimens or having received such regimens within the past 6 months were able to mount protective antibody responses to the influenza A(H1N1) 2009 virus vaccine Pandemrix during the 2009 "swine flu" pandemic. Contrary to the control group, where 82% responded adequately to the vaccine, none of the 67 patients achieved protective antibody titers, suggesting that lymphoma patients receiving rituximab-containing regimens might not benefit from this vaccine. It is important that doctors who care for such patients are aware that they may fail to respond not only to the influenza vaccine, but also to other common vaccines.     

Toxicity and response to thiopurines in patients with inflammatory bowel disease

The use of thiopurines is well established in the management of inflammatory bowel disease. A wealth of data and experience, amassed over several decades, supporting their efficacy has recently been challenged by trials that failed to show a benefit in Crohn’s disease when used early in the disease course, although other trials continue to support their role both as monotherapy and in combination with anti-TNF. Recent reports of previously unrecognized toxicity have also emerged. Fortunately, the absolute incidence of serious toxicity remains low, and an improved understanding of how best to minimize risk and the recognition of groups of patients at higher risk of toxicity from thiopurines means that they remain a relatively safe therapy in the majority of patients. In this paper, we review the literature evaluating the role of thiopurines in inflammatory bowel disease as well as their toxicity. We conclude that education regarding the spectrum of thiopurine side effects and optimal monitoring during therapy may help with optimizing safety and efficacy of these important medications.